Multiple System Atrophy

Size: px
Start display at page:

Download "Multiple System Atrophy"

Transcription

1 Multiple System Atrophy Multiple System Atrophy Felix Geser and Gregor K. Wenning INTRODUCTION Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder characterized clinically by various combinations of parkinsonian, autonomic, cerebellar, or pyramidal symptoms and signs and pathologically by cell loss, gliosis, and glial cytoplasmic inclusions in several brain and spinal cord structures. The term MSA was introduced in 1969, however cases of MSA were previously reported under the rubrics of striatonigral degeneration, olivopontocerebellar atrophy, Shy Drager syndrome and idiopathic orthostatic hypotension. In the late 1990s, α-synuclein immunostaining was recognized as most sensitive marker of inclusion pathology in MSA: because of these advances in molecular pathogenesis, MSA has been firmly established as α-synucleinopathy along with Parkinson s disease (PD) and dementia with Lewy bodies. Recent epidemiological surveys have shown that MSA is not a rare disorder (~5 cases per 100,000 population), and that misdiagnosis, especially with PD, is still common due to variable clinical presentations of MSA. However, the clinical picture of MSA in its full-blown form is distinctive. The patient is hypomimic with orofacial and anterior neck dystonia resulting in a grinning smile akin to risus sardonicus and sometimes disproportionate antecollis. The voice is often markedly impaired with a characteristic quivering high-pitched dysarthria. The motor disorder of MSA is often mixed with parkinsonism, cerebellar ataxia, limb dystonia, myoclonus, and pyramidal features occurring at the same time. However, akinesia and rigidity are the predominating features in 80% of patients, and cerebellar ataxia within the remaining 20%. According to the predominant motor presentation, MSA patients may be labeled as parkinsonian or cerebellar variant (MSA-P, MSA-C). The diagnosis of MSA is largely based on clinical expertise, and this is well illustrated by the consensus diagnostic criteria, which comprise clinical features only (divided into four domains including autonomic dysfunction, parkinsonism, cerebellar dysfunction, and corticospinal tract dysfunction). Nevertheless, several autonomic function, imaging, neurophysiological, and biochemical studies have been proposed in the last decade to help in the differential diagnosis of MSA. No drug treatment consistently benefits patients with this disease. Indeed, parkinsonism often shows a poor or unsustained response to chronic levodopa therapy, however, one-third of the patients may show a moderate-to-good dopaminergic response initially. There is no effective drug treatment for cerebellar ataxia. On the other hand, features of autonomic failure such as orthostatic hypotension, urinary retention or incontinence, constipation, and impotence, may often be relieved if recognized by the treating physician. Novel symptomatic and neuroprotective therapies are urgently required. From: Current Clinical Neurology: Atypical Parkinsonian Disorders Edited by: I. Litvan Humana Press Inc., Totowa, NJ 335

2 336 Geser and Wenning EPIDEMIOLOGY Descriptive Epidemiology There are only a few descriptive epidemiological studies on MSA. Bower and colleagues reported the incidence of MSA over a 14-yr period in Olmsted County, Minnesota. Nine incident cases of MSA were identified, none of which had an onset before the age of 50 yr. The reported crude incidence rate was 0.6 cases per 100,000 population per year; when the age band >50 yr was examined, the estimate rose to 3 cases per 100,000 population (1). Estimates of the prevalence of MSA (per 100,000 in the population) in five studies were 1.9 (2), 4.4 (3), 2.3 (4), 4.9 (5) and in individuals over 65 yr 310 (6). The last three studies did not specifically address the prevalence of MSA, the primary aim of the work being to assess the prevalence of PD. In the Western Europe population, estimated on the basis of Bower s study (1), 81.5% of the cases are concentrated in the 60- to 79-yr age band, whereas only 9.8% and 8.7% fall within the 50- to 59-yr and >80-yr age bands, respectively. These figures indicate a prevalence of MSA that is quite similar to that of other well-known neurological conditions such as Huntington s disease, myotonic dystrophy, and motor neuron disease. Analytical Epidemiology So far no single environmental factor has been clearly established as conferring increased or reduced risks to develop MSA. Only one case-control study, based on 60 MSA cases and 60 controls, has been published to date (7). This study revealed a higher risk of disease onset associated with occupational exposure to organic solvents, plastic monomers and additives, pesticides, and metals. Moreover, a higher frequency of symptoms and neurological diseases has been observed in first relatives of MSA cases than in controls. This last finding points to a genetic predisposition to neurological diseases. A review of consecutive medical records of 100 patients who satisfied the diagnostic Consensus criteria for MSA (8) showed that 11 patients had a notable history of heavy exposure to environmental toxins including malathion, diazinon, formaldehyde, n-hexane, benzene, methyl isobutyl ketone, and pesticides (9). Despite its methodical limits, this study implicates environmental factors in the pathogenesis of MSA. Smoking was less common among MSA patients compared to controls according to a cross-sectional study (10). Prospective case-control studies are needed to clarify whether smoking is a protective factor against MSA. CLINICAL DIAGNOSTIC CRITERIA Clinical diagnostic criteria for MSA were first proposed by Quinn in 1989 (11) and later slightly modified in 1994 (12). According to this schema, patients are classified as either striatonigral degeneration (SND) or olivopontocerebellar atrophy (OPCA) type MSA depending on the predominance of parkinsonism or cerebellar ataxia. There are three levels of diagnostic probability: possible, probable, and definite. Patients with sporadic adult-onset poorly levodopa-responsive parkinsonism fulfill criteria for possible SND. The presence of other atypical features such as severe autonomic failure, cerebellar or pyramidal signs, or a pathological sphincter electromyogram (EMG) is required for a diagnosis of probable SND. Patients with sporadic late-onset predominant cerebellar ataxia with additional mild parkinsonism or pyramidal signs are considered possible OPCA-type MSA. This may result in confusion since some patients with possible OPCA may also qualify for probable SND provided predominant cerebellar ataxia is accompanied by parkinsonian features. A diagnosis of probable OPCA-type MSA requires the additional presence of severe autonomic failure or a pathological sphincter EMG. A definite diagnosis rests on neuropathological confirmation. Predominant SND- or OPCA-type presentations may be distinguished from pure types on the basis of associated cerebellar (predominant SND) or parkinsonian features (predominant OPCA). Since some degree of

3 Multiple System Atrophy 337 autonomic failure is present in almost all SND- and OPCA-type MSA patients (13,14) a further autonomic subtype (Shy Drager syndrome) was not considered useful (15). A number of exclusion criteria were also proposed: onset should be age 30 yr or more, and in order to exclude inherited adult-onset ataxias there should be no family history of MSA. The validity of Quinn s criteria was evaluated in a clinicopathologic study by Litvan and coworkers. This study revealed the criteria for the diagnosis of MSA proposed by Quinn present a suboptimal specificity (79% for possible MSA and 97% for probable MSA, at the first visit), a low sensitivity (53% for possible MSA and 44% for probable MSA, at the first visit), and a predictive value of 30% for possible MSA and 68% for probable MSA (16). Because of the suboptimal diagnostic accuracy of Quinn s criteria, in 1998 an International Consensus Conference promoted by the American Academy of Neurology was convened to develop new and optimized criteria for a clinical diagnosis of MSA (Table 1) (8). The Consensus criteria are now widely used for a clinical diagnosis of MSA. These criteria specify three diagnostic categories of increasing certainty: possible, probable, and definite. The diagnosis of possible and probable MSA are based on the presence of clinical features listed in Table 1. In addition, exclusion criteria have to be considered. A definite diagnosis requires a typical neuropathological lesion pattern as well as deposition of α-synuclein-positive glial cytoplasmic inclusions. A subsequent study analyzed the agreement between Quinn s criteria and Consensus criteria in a clinical series of 45 MSA patients. Concordance was moderate for possible MSA and substantial for probable MSA (17). Moreover, four cases with probable (n = 2) or possible (n = 2) MSA according to Quinn s criteria were unclassifiable according to the Consensus criteria. A recent retrospective evaluation of the Consensus criteria on pathologically proven cases showed excellent positive predictive values (PPVs) for both possible (93%) and probable MSA (100%) at the first clinic visit; however, sensitivity for probable MSA was poor especially in early stages of the disease (16% at the first clinic visit) (18). Interestingly, the Consensus criteria and Quinn s criteria had similar PPVs. Whether the Consensus criteria will improve recognition of MSA patients especially in early disease stages needs to be investigated by prospective surveys with neuropathological confirmation in as many cases as possible. ONSET AND PROGRESSION MSA usually manifests in middle age (the median age of onset is 53), affects both sexes, and progresses relentlessly with a mean survival of 6 9 yr (13,19,20). MSA patients may present with akinetic-rigid parkinsonism that usually responds poorly to levodopa. This has been identified as the most important early clinical discriminator of MSA and PD (11,21 23), although a subgroup of MSA patients may show a good or, rarely, excellent, but usually short-lived, response to levodopa (24 26). Progressive ataxia, mainly involving gait, may also be the presenting feature of MSA (27,28). A cerebellar presentation of MSA appears to be more common than the parkinsonian variant in Japan compared to Western countries (29). Autonomic failure with symptomatic orthostatic hypotension and/or urogenital and gastrointestinal disturbance may accompany the motor disorder in up to 50% of patients at disease onset (20). Besides the poor response to levodopa, and the additional presence of pyramidal or cerebellar signs or autonomic failure as major diagnostic clues, certain other features ( red flags ) such as orofacial dystonia, stridor, or disproportionate antecollis (Fig. 1) may raise suspicion of MSA (11) (Table 2). Red flags often are early warning signs of MSA (30). MSA is a progressive disease characterized by the gradual accumulation of disability reflecting involvement of the systems initially unaffected. Thus, patients who present initially with extrapyramidal features commonly progress to develop autonomic disturbances, cerebellar disorders, or both (see video of an advanced MSA-P patient showing marked akinesia and rigidity as well as cerebellar incoordination, particularly of lower limbs). Conversely, patients who begin with symptoms of cerebellar dysfunction often progress to develop extrapyramidal or autonomic disorders, or both. Patients whose

4 Table 1 MSA Consensus Criteria A. Nomenclature of clinical domains, features (disease characteristics) and criteria (defining features or composite of features) used in the diagnosis of MSA Domain Criterion Feature Autonomic and urinary dysfunction Orthostatic fall in blood pressure Orthostatic hypotension (by 20 mmhg systolic or 10 mmhg diastolic) (by 30 mmhg systolic or 15 mmhg diastolic) or persistent urinary incontinence with erectile Urinary incontinence or incomplete bladder emptying dysfunction in men or both Parkinsonism Bradykinesia plus Bradykinesia (progressive reduction in speed and amplitude rigidity of voluntary movements during repetitive actions) or postural instability Rigidity or tremor Postural instability (loss of primary postural reflexes) Tremor (postural, resting, or both) Cerebellar dysfunction Gait ataxia plus Gait ataxia (wide-based stance with irregular steps) ataxic dysarthria or limb ataxia or sustained gaze-evoked nystagmus Ataxic dysarthria Limb ataxia Sustained gaze-evoked nystagmus Corticospinal tract dysfunction No defining features Extensor plantar responses with hyperreflexia B. Diagnostic categories of MSA Possible MSA-P Possible MSA-C Probable MSA-P Probable MSA-C Definite MSA Criterion for parkinsonism plus two features from separate other domains. A poor levodopa response qualifies already as one feature, hence only one additional feature is required. Criterion for cerebellar dysfunction plus two features from separate other domains. Criterion for autonomic failure/urinary dysfunction plus poorly levodopa-responsive parkinsonism. Criterion for autonomic failure/urinary dysfunction plus cerebellar dysfunction. Pathological confirmation: high density of α-synuclein-positive GCIs associated with degenerative changes in the nigrostriatal (SND) and olivopontocerebellar pathways (OPCA). Modified from ref. 8. Reproduced with kind permission from Whitehouse Publishing: Wenning and Geser, Diagnosis and treatment of multiple system atrophy: an update. ACNR 2004;3(6): Geser and Wenning

5 Multiple System Atrophy 339 Fig. 1. Disproportionate antecollis of a patient with MSA-P. symptoms initially are autonomic may later develop cerebellar, extrapyramidal, or both types of disorders. In a recent large study on 230 cases carried out in Japan, MSA-P patients had more rapid functional deterioration than MSA-C patients, but showed similar survival (29). INVESTIGATIONS The diagnosis of MSA still rests on the clinical history and neurological examination. Attempts have been made, however, to improve diagnostic accuracy through analysis of cerebrospinal fluid (CSF) and serum biomarkers, autonomic function tests, structural and functional neuroimaging and neurophysiological techniques.

6 340 Geser and Wenning Table 2 Red Flags : Warning Features of MSA a Motor Red Flags Definition Orofacial dystonia Pisa syndrome Disproportionate antecollis Jerky tremor Dysarthria Nonmotor Red Flags Abnormal respiration REM sleep behavior disorder Cold hands/feet Raynaud s phenomenon Emotional incontinence Atypical spontaneous or L-dopa-induced dystonia predominantly affecting orofacial muscles, occasionally resembling risus sardonicus of cephalic tetanus. Subacute axial dystonia with a severe tonic lateral flexion of the trunk, head, and neck (contracted and hypertrophic paravertebral muscles may be present). Chin-on-chest, neck can only with difficulty be passively and forcibly extended to its normal position. Despite severe chronic neck flexion, flexion elsewhere is minor. Irregular (jerky) postural or action tremor of the hands and/or fingers. Atypical quivering, irregular, severely hypophonic or slurring high-pitched dysarthria, which tends to develop earlier, be more severe, and be associated with more marked dysphagia compared to PD. Nocturnal (harsh or strained, high-pitched inspiratory sounds) or diurnal inspira tory stridor, involuntary deep inspiratory sighs/gasps, sleep apnea (arrest of breathing for 10 s), and excessive snoring (increase from premorbid level, or newly arising). Intermittent loss of muscle atonia and appearance of elaborate motor activity (striking out with arms in sleep often with talking/shouting) associated with dream mentation. Coldness and color change (purple/blue) of extremities not resulting from drugs with blanching on pressure and poor circulatory return. Painful white finger, which may be provoked by ergot drugs. Crying inappropriately without sadness or laughing inappropriately without mirth. a Excluding cardinal diagnostic features of MSA such as orthostatic hypotension, urinary incontinence/retention, levodopaunresponsive parkinsonism, cerebellar (ataxia) and pyramidal signs. Also excluding nonspecific features suggesting atypical parkinsonism such as rapid progression or early instability and falls. Reproduced with kind permission from John Wiley & Sons, Inc.: Wenning et al., Multiple system atrophy: an update. Mov Disord 2003;18(suppl 6): CSF Analysis Studies have attempted to identify biomarkers in the CSF to achieve early and accurate diagnosis, as well as to monitor response to treatment. Proteins in the CSF, including glial fibrillary acidic protein (GFAP) and neurofilament (NFL) protein have been studied. No difference was found in CSF concentrations of GFAP between patients with PD and MSA, but high concentrations of NFL seem to differentiate atypical parkinsonian disorders from PD (31). Furthermore, CSF-NFL and levodopa tests combined with discriminant analysis may contribute even better to the differential diagnosis of parkinsonian syndromes (32). Whereas the CSF-NFL and levodopa tests predicted 79 and 85% correct diagnoses (PD or non-pd [MSA and progressive supranuclear palsy PSP]) respectively, the combined test predicted 90% correct diagnoses. Hormonal Testing In vivo studies in MSA, which involved testing of the endocrine component of the central autonomic nervous systems (the hypothalamopituitary axis) with a variety of challenge procedures, provided evidence of impaired humoral responses of the anterior and the posterior part of the pituitary gland with impaired secretion of adrenocorticotropic hormone (ACTH) (33), growth hormone (34), and vasopressin/adh (35). Although these observations can be made in virtually all advanced patients, their prevalence during the early course of MSA is unknown.

7 Multiple System Atrophy 341 There is an ongoing debate about the diagnostic value of the growth hormone (GH) response to clonidine (CGH-test), a neuropharmacological assessment of central adrenoceptor function, in PD and MSA. Clonidine is a centrally active α2-adrenoceptor agonist that lowers blood pressure predominantly by reducing CNS (central nervous system) sympathetic outflow. In an early study, there was no increase in GH levels after clonidine in patients with MSA compared to those with PD or pure autonomic failure (36). Kimber and colleagues confirmed a normal serum GH increase in response to clonidine in 14 PD patients (without autonomic failure) and in 19 patients with pure autonomic failure, whereas there was no GH rise in 31 patients with MSA (34). However, these findings have been challenged subsequently (37). More studies in well-defined patient cohorts are needed before the clonidine challenge test can be recommended as a helpful diagnostic test in patients with suspected MSA. Autonomic Function Tests Autonomic function tests are a mandatory part of the diagnostic process and clinical follow-up in patients with MSA. Findings of severe autonomic failure early in the course of the disease make the diagnosis of MSA more likely, although the specificity in comparison to other neurodegenerative disorders is unknown in a single patient. Pathological results of autonomic function tests may account for a considerable number of symptoms in MSA patients and should prompt specific therapeutic steps to improve quality of life and prevent secondary complications like injuries owing to hypotensioninduced falls or ascending urinary infections. Cardiovascular Function A history of postural faintness or other evidence of orthostatic hypotension, e.g., neck ache on rising in the morning or posturally related changes of visual perception, should be sought in all patients in whom MSA is suspected. After taking a comprehensive history, testing of cardiovascular function should be performed. According the consensus statement of the American Autonomic Society and the American Academy of Neurology on the definition of orthostatic hypotension, pure autonomic failure, and MSA, a drop in systolic blood pressure (BP) of 20 mm Hg or more, or in diastolic BP of 10 mmhg or more, compared with baseline is defined as orthostatic hypotension (OH) and must lead to more specific assessment (38). This is based on continuous noninvasive measurement of blood pressure and heart rate during tilt table testing (39 41). Although abnormal cardiovascular test results may provide evidence of sympathetic and/or parasympathetic failure, they do not differentiate autonomic failure associated with PD vs MSA (42). In MSA, cardiovascular dysregulation appears to be caused by central rather than peripheral autonomic failure. During supine rest noradrenaline levels (representing postganglionic sympathethic efferent activity) are normal (43), and there is no denervation hypersensitivity, which indicates a lack of increased expression of adrenergic receptors on peripheral neurons (44). Uptake of the noradrenaline analog meta-iodobenzylguanidine is normal in postganglionic cardiac neurons (45 48) and the response to tilt is impaired with little increase in noradrenaline. In contrast, mainly postganglionic sympathetic dysfunction is thought to account for autonomic failure associated with PD. In keeping with this assumption, both basal and tilted noradrenaline levels are low. Bladder Function Assessment of bladder function is mandatory in MSA and usually provides evidence of involvement of the autonomic nervous system already at an early stage of the disease. Following a careful history regarding frequency of voiding, difficulties in initiating or suppressing voiding, and the presence and degree of urinary incontinence, a standard urine analysis should exclude an infection. Postvoid residual volume needs to be determined sonographically or via catheterization to initiate intermittent self-catheterization in due course. In some patients only cystometry can discriminate between hypocontractile detrusor function and a hyperreflexic sphincter-detrusor dyssynergy.

8 342 Geser and Wenning The nature of bladder dysfunction is different in MSA and PD. Although pollakiuria and urgency are common in both disorders, marked urge or stress incontinence with continuous leakage is not a feature of PD, apart from very advanced cases. Urodynamic studies show a characteristic pattern of abnormality in MSA patients (49). In the early stages there is often detrusor hyperreflexia, often with bladder neck incompetence resulting from abnormal urethral sphincter function, which result in early pollakiuria and urgency followed by urge incontinence. Later on, the ability to initiate a voluntary micturition reflex and the strength of the hyperreflexic detrusor contractions diminish, and the bladder may become atonic, accounting for increasing postmicturition residual urine volumes. The detrusor hyperreflexia may result from a disturbance of the pontine micturition center (50,51). Alternatively, degeneration of substantia nigra and other regions of the basal ganglia that are important in the control of micturition, may contribute to urological symptoms. The atonic bladder in advanced MSA has been related to the progressive degeneration of the intermediolateral columns of the thoracolumbar spinal cord (50), however, this remains speculative. IMAGING Magnetic Resonance Imaging (MRI) MRI scanning of patients with MSA often, but not always, reveals atrophy of cerebellar vermis and, less marked, of cerebellar hemispheres (52). There is also evidence of shrinkage of pons as well as middle cerebellar peduncles (27), differentiating MSA-C from cortical cerebellar atrophy (CCA). The pattern of infratentorial atrophy visible on MRI correlates with the pathological process of OPCA affecting the cerebellar vermis and hemispheres, middle cerebellar peduncles, pons, and lower brainstem (53). The MRI changes may be indistinguishable from those of patients with autosomal dominant cerebellar ataxias (54). MRI measures of basal ganglia pathology in MSA such as width of substantia nigra pars compacta, lentiform nucleus, and head of the caudate are less well established and naked-eye assessments are often unreliable. In advanced cases putaminal atrophy may be detectable and may correlate with severity of extrapyramidal symptoms (55). However, in one study MRIbased two-dimensional basal ganglia morphometry has proved unhelpful in the early differential diagnosis of patients with levodopa-unresponsive parkinsonism (56). A significant progression of atrophy to under the normal limit was observed in the cerebrum, frontal and temporal lobes, showing the involvement of the cerebral hemisphere, especially the frontal lobe (57). Abnormalities on MRI may include not only atrophy, but also signal abnormalities on T2-weighted images within the pontocerebellar system and putamen. Signal hyperintensities sometimes seen within the pons and middle cerebellar peduncles are thought to reflect degeneration of pontocerebellar fibers and therefore, together with marked atrophy in these areas, indicate a major site of pathology in OPCA type MSA (MSA-C) (27,58). The characteristic infratentorial signal change on T2-weighted 1.5 Tesla MRI ( hot cross bun sign) may also corroborate the clinical diagnosis of MSA (52). Putaminal hypointensities in supposedly atypical parkinsonian disorders (APDs) were first reported in 1986 by two groups using a 1.5 Tesla magnet and T2-weighted images (59,60). This change has subsequently been observed by others in cases clinically thought to have MSA (27,55,61), and in some cases with pathological confirmation (62 64). A lateral to medial as well as posterior to anterior gradient is also well established with the most prominent changes in the posterolateral putamen (55,60,62). This putaminal hypointensity has been proposed as a sensitive and specific abnormality in patients with MSA, and to reflect increased iron deposition. However, similar abnormalities may occur in patients with classical PD (65,66) or may represent incidental findings in patients without basal ganglia disorders (Wenning G, unpublished observations). The notion of increased iron deposition has been challenged by Brooks and colleagues (67) and later by Schwarz and colleagues (64). Recently it was shown that hypointense putaminal signal changes were more often observed in MSA than in PD patients using T2*-weighted gradient echo (GE) but not T2-weighted fast-spin echo images, indicating that T2*-weighted GE sequences are of diagnostic value for patients with parkinsonism (68).

9 Multiple System Atrophy 343 Increased putaminal relative to pallidal hypointensities may be seen as well as a slit-like hyperintense band lateral to the putamen (64,69 71). These changes are consistent with a clinical diagnosis of MSA. However, they appear to be nonspecific and have also been noted in clinically diagnosed PD and PSP (52,66). The pattern consisting of hypointense and hyperintense T2 changes within the putamen is a highly specific MRI sign of MSA, whereas hypointensity alone remains a sensitive, but nonspecific sign of MSA (72). The hyperintense signal correlated with the most pronounced reactive microgliosis and astrogliosis or highest iron content in MRI-postmortem studies (62,64). Konagaya et al. (73) reported that in a case of MSA, the slit hyperintensity at the putaminal margin represented widened intertissue space owing to a severe shrinkage and rarefaction of the putamen. However, in spite of these speculations the nature of this abnormal signal intensity remains uncertain. Diffusion-weighted imaging (DWI) may represent a useful diagnostic tool that can provide additional support for a diagnosis of MSA-P. DWI, even if measured in the slice direction only, is able to discriminate MSA-P and both patients with PD and healthy volunteers on the basis of putaminal radc (regional apparent diffusion coefficient) values (74). The increased putaminal radc values in MSA-P are likely to reflect ongoing striatal degeneration, whereas most neuropathologic studies reveal intact striatum in PD. But, since in PSP compared to PD patients radcs were also significantly increased in both putamen and globus pallidus (75), increased putaminal radc values do not discriminate MSA-P from PSP. Whether magnetic resonance volumetry will contribute to the differential diagnosis of MSA from other parkinsonian disorders remains to be confirmed. Schulz et al. (76) found significant reductions in mean striatal and brainstem volumes in patients with MSA-P, MSA-C, and PSP, whereas patients with MSA-C and MSA-P also showed a reduction in cerebellar volume. Total intracranial volumenormalized MRI-based volumetric measurements provide a sensitive marker to discriminate typical and atypical parkinsonism. Voxel-based morphometry (VBM) confirmed previous region of interest (ROI)-based volumetric studies (76) showing basal ganglia and infratentorial volume loss in MSA-P patients (77). These data revealed prominent cortical volume loss in MSA-P mainly comprising the cortical targets of striatal projections such as the primary sensorimotor, lateral premotor cortices, and the prefrontal cortex, but also the insula. These changes are consistent with the established frontal lobe impairment of MSA patients (78). Proton magnetic resonance spectroscopy (MRS) is a noninvasive method that provides information about the chemical pathology of disorders affecting the CNS. MRS has been used to identify striatal metabolic changes in MSA (79 82). However, the available data are conflicting and further studies are clearly required to establish the role of MRS in the diagnosis of MSA. Functional Imaging Single-photon emission tomography (SPECT) or positron emission tomography (PET) studies of patients with MSA-P have demonstrated the combined nigral and striatal pathology using [( 123 )I]β-CIT [2β-carboxymethoxy-3β-(4-iodophenyl)tropane] (SPECT) or [ 10 F]fluorodopa (PET) and a variety of postsynaptic dopamine or opiate receptor ligands such as [ 123 I]iodobenzamide (IBZM) (SPECT), [ 11 C]raclopride or [ 11 C]diprenorphin (PET). The Hammersmith Cyclotron Unit, using PET, found that putaminal uptake of the presynaptic dopaminergic markers [ 18 F]fluorodopa and S-[ 11 C]nomifensine (83 85) was similarly reduced in MSA and PD; in approximately half the MSA subjects, caudate uptake was also markedly reduced, as opposed to only moderate reduction in PD. However, discriminant function analysis of striatal [ 18 F]fluorodopa uptake separated MSA and PD patients poorly (85). Patients with PD, PSP, and MSA share a marked loss of fluorodopa uptake in the putamen; however, uptake in the caudate nucleus differs among the three groups, with patients who have MSA showing uptake rates intermediate between those of patients with PD (normal uptake) and with PSP (markedly reduced uptake) (83). Measurements of striatal dopamine D 2 receptor densities using raclopride and PET failed to differentiate between idiopathic and atypical parkinsonism, demonstrating a similar loss of densities

10 344 Geser and Wenning in levodopa-treated patients with fluctuating PD, MSA, and PSP (86). PET studies using other ligands such as [ 11 C]diprenorphine (nonselective opioid receptor antagonist) (87) and [ 18 F]fluorodeoxyglucose (88 90) have proved more consistent in detecting striatal degeneration and in distinguishing patients with MSA-P from those with PD, particularly when combined with a dopamine D2 receptor scan (91,92). Widespread functional abnormalities in MSA-C have been demonstrated using [ 18 F]fluorodeoxyglucose and PET (93). Reduced metabolism was most marked in the brainstem and cerebellum, but other areas such as the putamen, caudate nucleus, thalamus, and cerebral cortex were also involved, differentiating MSA-C from spinocerebellar ataxias (SCAs). Subclinical evidence of striatal pathology in MSA-C, in the absence of extrapyramidal features, has been demonstrated using the nonselective opioid receptor ligand diprenorphine and PET (94). In a PET study using [ 18 F]fluorodeoxyglucose, in comparison with normal controls putaminal hypometabolism was absent in sporadic OPCA patients without autonomic failure and extrapyramidal features, but present in those who were classified as OPCA-type MSA and therefore had autonomic dysfunction with or without parkinsonian features at the time of examination (93). Striatal opiate receptors are reduced not only in MSA-P (87) but also in MSA-C with associated autonomic failure (94) supporting its nosological status as the cerebellar subtype of MSA. Differences in cerebellar benzodiazepine receptor binding densities have also been shown in MSA-C, CCA, and SCA using [ 11 C]flumazenil and PET (95). Additionally, the poor levodopa response may be related to a deficiency in striatal D 1 receptor binding, as shown by PET studies in clinically diagnosed patients with MSA using the ligand [ 11 C]SCH (96). This is a potentially helpful observation that may aid early differentiation of MSA and PD if corroborated by other groups. SPECT imaging studies of patients with dopa naive parkinsonism have used [ 123 I]iodobenzamide (IBZM) as D2 receptor ligand (21,22). A good response to apomorphine and subsequent benefit from chronic dopaminergic therapy was observed in subjects with normal IBZM binding whereas subjects with reduced binding failed to respond. Some of these patients developed other atypical clinical features suggestive of MSA during follow-up (97). Other SPECT studies have also revealed significant reductions of striatal IBZM binding in clinically probable MSA subjects compared to PD patients (27,98). Since [ 123 I]β-CIT SPECT reliably enables the visualization of the presynaptic dopaminergic lesion, this method was used as a label of dopamine transporter (DAT) to study the progression of presynaptic dopaminergic degeneration in PD and APD including MSA by Pirker and coworkers (99). The results of the sequential [ 123 I]β-CIT SPECT imaging demonstrate a rapid decline of striatal β-cit binding in patients with APD, exceeding the reduction in PD. Scintigraphic visualization of postganglionic sympathetic cardiac neurons was found to differentiate patients with MSA from patients with PD (45 48), because patients in the latter group show a severely reduced cardiac uptake of the radioactive ligand [ 123 I]metaiodobenzylguanidine (MIBG). This method appears to be a highly sensitive and specific tool to discriminate between MSA and PD already within 2 year of onset of symptoms; however, the test cannot distinguish MSA from other APD such as PSP (100). NEUROPHYSIOLOGICAL TECHNIQUES The external anal or urethral sphincter electromyogram (EMG) is a useful investigation in patients with suspected MSA. Because of degeneration of Onuf s nucleus, both anal and urethral external sphincter muscles undergo denervation and re-innervation. Abnormality of the striated urethral sphincter EMG in MSA was first shown by Martinelli and Coccagna in 1978 (101). Subsequently, Kirby and colleagues (49) confirmed the presence of polyphasia and abnormal prolongation of individual motor units in MSA, and also examined the potential diagnostic role of sphincter EMG in patients with MSA and PD (102). Sixteen (62%) of 26 patients with probable MSA, and only 1 (8%) of 13 with probable PD had a pathological EMG result (sensitivity 0.62, specificity 0.92). This test

11 Multiple System Atrophy 345 also helps to identify patients in whom incontinence may develop or worsen following surgery. Anal sphincter EMG is generally better tolerated, and yields identical results (50). In at least 80% of patients with MSA, EMG of the external anal sphincter reveals signs of neuronal degeneration in Onuf s nucleus with spontaneous activity and increased polyphasia ( ). However, these findings do not reliably differentiate between MSA and other forms of APD. An abnormal anal sphincter examination was present in 5 of 12 (41.6%) PSP patients (106). Furthermore, neurogenic changes of external anal sphincter muscle have also been demonstrated in advanced stages of PD by several investigators (107,108). Also chronic constipation, previous pelvic surgery, or vaginal deliveries can be confounding factors to induce nonspecific abnormalities (109). In summary, in patients with probable MSA, abnormal sphincter EMG, as compared to control subjects, has been found in the vast majority of patients, including those who, as yet, have no urological or anorectal problems. The prevalence of abnormalities in the early stages of MSA is as yet unclear. Patients with PD as a rule do not show severe sphincter EMG abnormalities in the early stage of the disease, unless other causes for sphincter denervation are present. However, sphincter EMG does not distinguish MSA from PSP (110). For these reasons, this examination has not been included in the guidelines suggested by the Consensus Conference (8). In general, the value of evoked potential studies in the diagnosis of MSA is limited. Magnetic evoked potentials are often, but not always, normal in MSA (111,112). Somatosensory, visual, and acoustic evoked potentials may show prolonged latencies in up to 40% of patients, but most patients show no abnormalities of central efferent and afferent neuronal pathways ( ). Some investigators (115,116) have suggested that both somatic anterior horn cells and peripheral nerves are commonly affected in MSA, and their involvement has therefore been regarded as part of the clinical spectrum of MSA. Abnormalities of nerve conduction studies seem to be more frequent in MSA-P (43%) compared to MSA-C (14%), suggesting that the peripheral nervous system is differentially affected in the motor presentations of this disorder (117). Excessive auditory startle responses (ASRs) may also help differentiate MSA both from PD and other forms of APD (118). Exaggerated ASRs may reflect disinhibition of lower brainstem nuclei owing to the degenerative disorder. ASRs appear to be more disinhibited in MSA-P than MSA-C, and there is a lack of ASR habituation in MSA-C unlike MSA-P, suggesting involvement of different neural structures in the two MSA-subtypes (119). PATHOLOGY In MSA-P, the striatonigral system is the main site of pathology but less severe degeneration can be widespread and usually includes the olivopontocerebellar system (51). The putamen is shrunken with gray-green discoloration. When putaminal pathology is severe there may be a cribriform appearance. In early stages the putaminal lesion shows a distinct topographical distribution with a predilection for the caudal and dorsolateral regions (120). Later on during the course of disease, the entire putamen is usually affected with the result that bundles of striatopallidal fibres are narrowed and poorly stained for myelin. Degeneration of pigmented nerve cells occurs in the substantia nigra pars compacta (SNC), whereas nonpigmented cells of the pars reticulata are reported as normal. The topographical patterns of neurodegeneration involving the motor neostriatum, efferent pathways, and nigral neurons, reflect their anatomical relationship and suggest a common denominator or linked degeneration (120). In MSA-C, the brunt of pathology is in the olivopontocerebellar system whereas the involvement of striatum and substantia nigra is less severe. The basis pontis is atrophic, with loss of pontine neurons and transverse pontocerebellar fibers. In sections stained for myelin, the intact descending corticospinal tracts stand out against the degenerated transverse fibers and the atrophic middle cer-

12 346 Geser and Wenning ebellar peduncles. There is a disproportionate depletion of fibers from the middle cerebellar peduncles compared with the loss of pontine neurons, an observation consistent with a dying back process. A supraspinal contribution to the autonomic failure of MSA is now well established. Cell loss is reported in dorsal motor nucleus of the vagus (121) and involves catecholaminergic neurons of ventrolateral medulla (122). It has also been described for the Edinger Westphal nucleus and posterior hypothalamus (123) including the tuberomamillary nucleus (124). Papp and Lantos (125) have shown marked involvement of brainstem pontomedullary reticular formation with glial cytoplasmic inclusions (GCIs), providing a supraspinal histological counterpart for impaired visceral function. Autonomic neuronal degeneration affects the locus ceruleus, too (20). Disordered bladder, rectal, and sexual function in MSA-P and MSA-C have also been associated with cell loss in parasympathetic preganglionic nuclei of the spinal cord. These neurons are localized rostrally in the Onuf s nucleus between the sacral segments S2 and S3 and more caudally in the inferior intermediolateral nucleus chiefly in the S3 to S4 segments (126). Degeneration of sympathetic preganglionic neurones in the intermediolateral column of the thoracolumbar spinal cord is considered contributory to orthostatic hypotension. If one considers only those reports in which formal cell counts have been made, with very few exceptions all cases of MSA with predominant pathology in either the striatonigral or olivopontocerebellar system show loss of intermediolateral cells (127). However, it is noteworthy that there is not always a strong correlation between nerve cell depletion or gliosis and the clinical degree of autonomic failure. It is estimated that more than 50% of cells within the intermediolateral column need to decay before symptoms become evident (128). In the peripheral component of the autonomic nervous system, Bannister and Oppenheimer have described atrophy of the glossopharyngeal and vagus nerves (129). A variety of other neuronal populations are noted to show cell depletion and gliosis with considerable differences in vulnerability from case to case. Only a few of the reported lesions are discussed here. Various degree of abnormalities in the cerebral hemisphere, including Betz cell loss, were detected in pathologically proven MSA cases (57, ). Furthermore, anterior horn cells may show some depletion but rarely to the same extent as that occurring in motor neuron disease (126,133). Depletion of large myelinated nerve fibres in the recurrent laryngeal nerve that innervates intrinsic laryngeal muscles has been demonstrated in MSA patients with vocal cord palsy (134). From a neuropathological viewpoint, there is little cause for confusion of MSA with other neurodegenerative conditions. The GCI is the hallmark that accompanies the signs of degeneration involving striatonigral and olivopontocerebellar systems. GCIs are distinctly different from filamentous oligodendroglial inclusions, called coiled bodies, found in other neurodegenerative diseases, including PSP, CBD, and argyrophilic grain disease ( ). Rarely MSA may be combined with additional pathologies. Lewy bodies (LBs) have been reported in 8 10% of MSA cases and show a distribution comparable with that of PD (139). This frequency is similar to that of controls and suggests an incidental finding related to ageing and/or presymptomatic PD. The discovery of GCIs in MSA brains in 1989 highlighted the unique glial pathology as biological hallmark of this disorder (140). GCIs are argyrophilic and half-moon, oval, or conical in shape (141) and are composed of 20- to 30-nm tubular filaments (142). Although inclusions have been described in five cellular sites, i.e., in oligodendroglial and neuronal cytoplasm and nuclei as well as in axons (143), GCIs (140) are most ubiquitous and appear to represent the subcellular hallmark lesion of MSA (141). Their distribution selectively involves basal ganglia, supplementary and primary motor cortex, the reticular formation, basis pontis, the middle cerebellar peduncles, and the cerebellar white matter (125,141). GCIs contain classical cytoskeletal antigens, including ubiquitin and tau (141,144). More recently, α-synuclein immunoreactivity has been recognized as the most sensitive marker of GCIs (145) (Fig. 2). In fact, α-synuclein, a presynaptic protein that is affected by point mutations in some families with autosomal dominant PD (146) and that is present in LBs (147), has also been observed in both neuronal inclusions and GCIs ( ) in brains of patients with MSA. GCI filaments are multilayered in structure, with α-synuclein oligomers forming the central core fibrils of the

13 Multiple System Atrophy 347 Fig. 2. α-synuclein immunostaining reveals GCIs in subcortical white matter. Courtesy of Prof. K. Jellinger. Reproduced with kind permission of Whitehouse Publishing. Diagnosis and treatment of multiple system atrophy: an update. ACNR 2004;3(6):5 10. filaments (142). The accumulation of α-synuclein into filamentous inclusions appears to play a key role not only in MSA, but also in a growing number of α-synucleinopathies such as PD, dementia with Lbs (DLB), Down syndrome, familial Alzheimer s disease (AD), and sporadic AD (153). The α-synuclein accumulation in GCIs as well as in neuronal inclusions associated with MSA precedes their ubiquitination (154). Importantly, α-synuclein, but not ubiquitin, antibodies also reveal numerous degenerating neurites in the white matter of MSA cases (154). This suggests that an as yet unrecognised degree of pathology may be present in the axons of MSA cases, although whether neuronal/axonal α-synuclein pathology precedes glial α-synuclein pathology has not been examined. Recent findings support an important role for glial cells and inflammatory reactions in many neurodegenerative diseases including PD, DLB, and MSA ( ). Neuronal survival is critically dependent on glial function, which can exert both neuroprotective and neurotoxic influences. Glial cells are a primary target of cytokines and are activated in response to many cytokines, including tumor necrosis factor (TNF)-α (158). This activation can trigger further release of cytokines that might enhance or suppress local inflammatory responses and neuronal survival. These cytokines may also participate in neurodegeneration either indirectly by activating other glial cells or directly by inducing apoptosis ( ). Several studies indicated that TNF-α is toxic for dopaminergic neurons in vitro (162) and in vivo (163), thus supporting the potential involvement of this pro-inflammatory cytokine in the neurodegenerative processes in PD and other α-synucleinopathies. However, the relationship between intracellular α-synuclein-positive inclusions and the proinflammatory response in α-synucleinopathies remains obscure. The activation of microglial cells may be the final common pathway, contributing both to demyelination and neuronal removal, irrespective of the mode of cell death. PK selectively binds to benzodiazepine sites on activated microglia. 11 C PK PET has demonstrated activated microglia in vivo in the putamen, pallidum, substantia nigra, and pontine region in five patients with MSA (164).

14 348 Geser and Wenning Fig. 3. Partial restored responsiveness to apomorphine following embryonic transplantation in the double lesion rat model. The left figure shows apomorphine induced rotation rates following the double lesion as well as transplantation of embryonic striatal, mesencephalic, combined striatal-mesencephalic, and sham grafts. The figure on the right shows surviving embryonic graft tissue, expressing Dopamin-D2 receptors (red spots) within a severely lesion host striatum, compared to a sham graft without evidence of regeneration. Modified from ref Fig. 3. Regeneration of apomorphine responsiveness following embryonic transplantation in the double lesion SND rat model as shown by behavioral studies and D-2 receptor autoradiography. (A) shows increased apomorphine-induced rotation rates following transplantation of embryonic striatal tissue (line marked with an asterisk) compared to nonsignificant changes in other transplant groups as well as sham controls (6-OHDA, 6- hydroxydopamine; QA, quinolinic acid; TP, transplantation; W, weeks). (B) shows surviving embroynic striatal graft tissue expressing foci of dompamine D-2 receptors (small arrows) within a severely lesioned host striatum, compared to a sham graft without evidence of regeneration (C). Modified from ref ANIMAL MODELS A number of in vivo MSA models have become available as preclinical test bed for novel therapeutic interventions. Based on experiments in the early 1990s (165), several attempts have been made to reproduce the core pathology of striatonigral degeneration (SND) that underlies L-Dopaunresponsive parkinsonism in MSA-P (166). The goal of these experimental studies was to replicate the unique lesion pattern present in human MSA-P/SND, i.e., the combined degeneration of dopam-

15 Multiple System Atrophy 349 inergic nigrostriatal pathways as well as corresponding striatal projections. This work utilized wellestablished nigral and striatal lesion models that had been developed to mimic the core pathology of PD and Huntington s disease. These experiments produced several models mimicking various degrees of disease severity, each having its own advantages and pitfalls (165, ). Embryonic striatal grafts have been shown to partially regenerate responsiveness to dopaminergic stimulation (177) (see Fig. 3) in the unilateral double lesion rat model. One principal problem encountered with the unilateral stereotaxic rat model was the interaction between the nigral and striatal lesion placement. Also the behavioral and motor impairments obtained were remote from those observed in the human disease. This was one of the reasons to move to a systemic primate model using the PD-like toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and the HD-like toxin, 3-nitropropionic acid (3-NP). This strategy generated a reproducible symptomatology closer to human MSA-P/SND, i.e., levodopa-unresponsive parkinsonism/dystonia correlated with striatal outflow pathway lesions and severe nigral degeneration (173,174). However, because of ethical considerations, time-consuming experiments, and the need for a great number of animals owing to a marked interindividual susceptibility to these mitochondrial toxins, the model strategy was switched to systemic MPTP + 3-NP mouse models (171,172). These models allow screening of drugs in sufficient number of animals. The systemic double toxin paradigm may also be applied to transgenic mice with targeted expression of α-synuclein in oligodendrocytes (175). However, more work is needed to confirm the stability of α-synuclein expression in these animals and particularly its deleterious effects upon oligodendroglial and neuronal function. TREATMENT Autonomic Failure Unfortunately there is no causal therapy of autonomic dysfunction available. Therefore the therapeutic strategy is defined by clinical symptoms and impairment of quality of life in these patients. Because of the progressive course of MSA, a regular review of the treatment is mandatory to adjust measures according to clinical needs. The concept to treat symptoms of orthostatic hypotension is based on the increase of intravascular volume and the reduction of volume shift to lower body parts when changing to upright position. The selection and combination of the following options depend on the severity of symptoms and their practicability in the single patient, but not on the extent of blood pressure drop during tilt test. Nonpharmacological options include sufficient fluid intake, high salt diet, more frequent, but smaller meals per day to reduce postprandial hypotension by spreading the total carbohydrate intake, and custom-made elastic body garments. During the night, head-up tilt increases intravascular volume up to 1 L within a week, which is particularly helpful to improve hypotension early in the morning. This approach is successful in particular in combination with fludrocortisone, which further supports sodium retention. The next group of drugs to consider are the sympathomimetics. These include ephedrine (with both direct and indirect effects), which is often valuable in central autonomic disorders such as MSA. With higher doses, side effects include tremulousness, loss of appetite, and urinary retention in men. Among the large number of vasoactive agents that have been evaluated in MSA, only one, the directly acting α-adrenergic agonist midodrine, meets the criteria of evidence-based medicine ( ). Side effects are usually mild and only rarely lead to discontinuation of treatment because of urinary retention or pruritus, predominantly on the scalp. Another promising drug appears to be the norepinephrine precursor L-threo-dihydroxyphenylserine (L-threo-DOPS), which has been used in this indication in Japan for years and efficacy of which has now been shown by a recent open, dose-finding trial (181). In case the above-mentioned drugs do not produce the desired effects, selective targeting is needed. The somatostatin analog, octreotide, is often beneficial in postprandial hypotension (182), presum-

Atypical parkinsonism

Atypical parkinsonism Atypical parkinsonism Wassilios Meissner Service de neurologie et CMR atrophie multisystématisée, CHU de Bordeaux Institut des Maladies Neurodégénératives, Université Bordeaux 2, CNRS UMR 5293 Parkinsonism?

More information

Pietro Cortelli. IRCCS Istituto delle Scienze Neurologiche di Bologna DIBINEM, Alma Mater Studiorum - Università di Bologna

Pietro Cortelli. IRCCS Istituto delle Scienze Neurologiche di Bologna DIBINEM, Alma Mater Studiorum - Università di Bologna Pietro Cortelli IRCCS Istituto delle Scienze Neurologiche di Bologna DIBINEM, Alma Mater Studiorum - Università di Bologna HYSTORY 1900 description of OPCA (Dejerine, Thomas) 1960 description of Shy-Drager

More information

DIFFERENTIAL DIAGNOSIS SARAH MARRINAN

DIFFERENTIAL DIAGNOSIS SARAH MARRINAN Parkinson s Academy Registrar Masterclass Sheffield DIFFERENTIAL DIAGNOSIS SARAH MARRINAN 17 th September 2014 Objectives Importance of age in diagnosis Diagnostic challenges Brain Bank criteria Differential

More information

III./3.1. Movement disorders with akinetic rigid symptoms

III./3.1. Movement disorders with akinetic rigid symptoms III./3.1. Movement disorders with akinetic rigid symptoms III./3.1.1. Parkinson s disease Parkinson s disease (PD) is the second most common neurodegenerative disorder worldwide after Alzheimer s disease.

More information

Niall Quinn. Professor of Clinical Neurology UCL IoN & NHNN Queen Square London UK

Niall Quinn. Professor of Clinical Neurology UCL IoN & NHNN Queen Square London UK Niall Quinn Professor of Clinical Neurology UCL IoN & NHNN Queen Square London UK Decade of the basal ganglia 1960 Shy Drager syndrome 1961 Striatonigral degeneration 1961 Birkmeyer & Hornykiewicz; Barbeau

More information

Pathogenesis of Degenerative Diseases and Dementias. D r. Ali Eltayb ( U. of Omdurman. I ). M. Path (U. of Alexandria)

Pathogenesis of Degenerative Diseases and Dementias. D r. Ali Eltayb ( U. of Omdurman. I ). M. Path (U. of Alexandria) Pathogenesis of Degenerative Diseases and Dementias D r. Ali Eltayb ( U. of Omdurman. I ). M. Path (U. of Alexandria) Dementias Defined: as the development of memory impairment and other cognitive deficits

More information

FDG-PET e parkinsonismi

FDG-PET e parkinsonismi Parkinsonismi FDG-PET e parkinsonismi Valentina Berti Dipartimento di Scienze Biomediche, Sperimentali e Cliniche Sez. Medicina Nucleare Università degli Studi di Firenze History 140 PubMed: FDG AND parkinsonism

More information

Neurodegenerative Disease. April 12, Cunningham. Department of Neurosciences

Neurodegenerative Disease. April 12, Cunningham. Department of Neurosciences Neurodegenerative Disease April 12, 2017 Cunningham Department of Neurosciences NEURODEGENERATIVE DISEASE Any of a group of hereditary and sporadic conditions characterized by progressive dysfunction,

More information

Multiple choice questions: ANSWERS

Multiple choice questions: ANSWERS Multiple choice questions: ANSWERS Chapter 1. Redefining Parkinson s disease 1. Common non-motor features that precede the motor findings in Parkinson s disease (PD) include all of the following except?

More information

Lecture XIII. Brain Diseases I - Parkinsonism! Brain Diseases I!

Lecture XIII. Brain Diseases I - Parkinsonism! Brain Diseases I! Lecture XIII. Brain Diseases I - Parkinsonism! Bio 3411! Wednesday!! Lecture XIII. Brain Diseases - I.! 1! Brain Diseases I! NEUROSCIENCE 5 th ed! Page!!Figure!!Feature! 408 18.9 A!!Substantia Nigra in

More information

Drunk When You re Not A 67 year old male presents with feeling off balance

Drunk When You re Not A 67 year old male presents with feeling off balance Drunk When You re Not A 67 year old male presents with feeling off balance Kiera McElrone, DO Internal Medicine/Pediatrics Residency Maine Medical Center September 2017 ACP Bar Harbor Meeting Chief Complaint

More information

biological psychology, p. 40 The study of the nervous system, especially the brain. neuroscience, p. 40

biological psychology, p. 40 The study of the nervous system, especially the brain. neuroscience, p. 40 biological psychology, p. 40 The specialized branch of psychology that studies the relationship between behavior and bodily processes and system; also called biopsychology or psychobiology. neuroscience,

More information

COGNITIVE SCIENCE 107A. Motor Systems: Basal Ganglia. Jaime A. Pineda, Ph.D.

COGNITIVE SCIENCE 107A. Motor Systems: Basal Ganglia. Jaime A. Pineda, Ph.D. COGNITIVE SCIENCE 107A Motor Systems: Basal Ganglia Jaime A. Pineda, Ph.D. Two major descending s Pyramidal vs. extrapyramidal Motor cortex Pyramidal system Pathway for voluntary movement Most fibers originate

More information

Multiple System Atrophy

Multiple System Atrophy Multiple System Atrophy This document has been prepared to help you become more informed about Multiple System Atrophy. It is designed to answer questions about the condition and includes suggestions on

More information

Imaging biomarkers for Parkinson s disease

Imaging biomarkers for Parkinson s disease 3 rd Congress of the European Academy of Neurology Amsterdam, The Netherlands, June 24 27, 2017 Teaching Course 6 MDS-ES/EAN: Neuroimaging in movement disorders - Level 2 Imaging biomarkers for Parkinson

More information

MULTI SYSTEM ATROPHY: REPORT OF TWO CASES Dipu Bhuyan 1, Rohit Kr. Chandak 2, Pankaj Kr. Patel 3, Sushant Agarwal 4, Debjanee Phukan 5

MULTI SYSTEM ATROPHY: REPORT OF TWO CASES Dipu Bhuyan 1, Rohit Kr. Chandak 2, Pankaj Kr. Patel 3, Sushant Agarwal 4, Debjanee Phukan 5 MULTI SYSTEM ATROPHY: REPORT OF TWO CASES Dipu Bhuyan 1, Rohit Kr. Chandak 2, Pankaj Kr. Patel 3, Sushant Agarwal 4, Debjanee Phukan 5 HOW TO CITE THIS ARTICLE: Dipu Bhuyan, Rohit Kr. Chandak, Pankaj Kr.

More information

Chapter 8. Control of movement

Chapter 8. Control of movement Chapter 8 Control of movement 1st Type: Skeletal Muscle Skeletal Muscle: Ones that moves us Muscles contract, limb flex Flexion: a movement of a limb that tends to bend its joints, contraction of a flexor

More information

By Dr. Saeed Vohra & Dr. Sanaa Alshaarawy

By Dr. Saeed Vohra & Dr. Sanaa Alshaarawy By Dr. Saeed Vohra & Dr. Sanaa Alshaarawy 1 By the end of the lecture, students will be able to : Distinguish the internal structure of the components of the brain stem in different levels and the specific

More information

Differential Diagnosis of Hypokinetic Movement Disorders

Differential Diagnosis of Hypokinetic Movement Disorders Differential Diagnosis of Hypokinetic Movement Disorders Dr Donald Grosset Consultant Neurologist - Honorary Professor Institute of Neurological Sciences - Glasgow University Hypokinetic Parkinson's Disease

More information

VL VA BASAL GANGLIA. FUNCTIONAl COMPONENTS. Function Component Deficits Start/initiation Basal Ganglia Spontan movements

VL VA BASAL GANGLIA. FUNCTIONAl COMPONENTS. Function Component Deficits Start/initiation Basal Ganglia Spontan movements BASAL GANGLIA Chris Cohan, Ph.D. Dept. of Pathology/Anat Sci University at Buffalo I) Overview How do Basal Ganglia affect movement Basal ganglia enhance cortical motor activity and facilitate movement.

More information

Damage on one side.. (Notes) Just remember: Unilateral damage to basal ganglia causes contralateral symptoms.

Damage on one side.. (Notes) Just remember: Unilateral damage to basal ganglia causes contralateral symptoms. Lecture 20 - Basal Ganglia Basal Ganglia (Nolte 5 th Ed pp 464) Damage to the basal ganglia produces involuntary movements. Although the basal ganglia do not influence LMN directly (to cause this involuntary

More information

ORIGINAL CONTRIBUTION. Brain Magnetic Resonance Imaging in Multiple-System Atrophy and Parkinson Disease

ORIGINAL CONTRIBUTION. Brain Magnetic Resonance Imaging in Multiple-System Atrophy and Parkinson Disease Brain Magnetic Resonance Imaging in Multiple-System Atrophy and Parkinson Disease A Diagnostic Algorithm ORIGINAL CONTRIBUTION Kirsty Bhattacharya, MD; Daniela Saadia, MD; Barbara Eisenkraft, MD; Melvin

More information

A. General features of the basal ganglia, one of our 3 major motor control centers:

A. General features of the basal ganglia, one of our 3 major motor control centers: Reading: Waxman pp. 141-146 are not very helpful! Computer Resources: HyperBrain, Chapter 12 Dental Neuroanatomy Suzanne S. Stensaas, Ph.D. April 22, 2010 THE BASAL GANGLIA Objectives: 1. What are the

More information

Strick Lecture 4 March 29, 2006 Page 1

Strick Lecture 4 March 29, 2006 Page 1 Strick Lecture 4 March 29, 2006 Page 1 Basal Ganglia OUTLINE- I. Structures included in the basal ganglia II. III. IV. Skeleton diagram of Basal Ganglia Loops with cortex Similarity with Cerebellar Loops

More information

Movement Disorders. Psychology 372 Physiological Psychology. Background. Myasthenia Gravis. Many Types

Movement Disorders. Psychology 372 Physiological Psychology. Background. Myasthenia Gravis. Many Types Background Movement Disorders Psychology 372 Physiological Psychology Steven E. Meier, Ph.D. Listen to the audio lecture while viewing these slides Early Studies Found some patients with progressive weakness

More information

International Journal of Health Sciences and Research ISSN:

International Journal of Health Sciences and Research  ISSN: International Journal of Health Sciences and Research www.ijhsr.org ISSN: 2249-9571 Case Report Multiple System Atrophy-Cerebellar Type (MSA-C): A Case Report Mohd Abbas Ilyas, Pramod Shaha, Kulamani Sahoo,

More information

Update on functional brain imaging in Movement Disorders

Update on functional brain imaging in Movement Disorders Update on functional brain imaging in Movement Disorders Mario Masellis, MSc, MD, FRCPC, PhD Assistant Professor & Clinician-Scientist Sunnybrook Health Sciences Centre University of Toronto 53 rd CNSF

More information

Parkinson s Disease. Prevalence. Mark S. Baron, M.D. Cardinal Features. Clinical Characteristics. Not Just a Movement Disorder

Parkinson s Disease. Prevalence. Mark S. Baron, M.D. Cardinal Features. Clinical Characteristics. Not Just a Movement Disorder Prevalence Parkinson s Disease Mark S. Baron, M.D. Associate Professor of Neurology Movement Disorders Section VCU School of Medicine Common disorder Approaching 1% by 65 yrs of age, 2% by 80 yrs of age

More information

Movement Disorders: A Brief Overview

Movement Disorders: A Brief Overview Movement Disorders: A Brief Overview Albert Hung, MD, PhD Massachusetts General Hospital Harvard Medical School August 17, 2006 Cardinal Features of Parkinsonism Tremor Rigidity Bradykinesia Postural imbalance

More information

A. General features of the basal ganglia, one of our 3 major motor control centers:

A. General features of the basal ganglia, one of our 3 major motor control centers: Reading: Waxman pp. 141-146 are not very helpful! Computer Resources: HyperBrain, Chapter 12 Dental Neuroanatomy Suzanne S. Stensaas, Ph.D. March 1, 2012 THE BASAL GANGLIA Objectives: 1. What are the main

More information

Parkinson s Disease in the Elderly A Physicians perspective. Dr John Coyle

Parkinson s Disease in the Elderly A Physicians perspective. Dr John Coyle Parkinson s Disease in the Elderly A Physicians perspective Dr John Coyle Overview Introduction Epidemiology and aetiology Pathogenesis Diagnosis and clinical features Treatment Psychological issues/ non

More information

DISORDERS OF THE MOTOR SYSTEM. Jeanette J. Norden, Ph.D. Professor Emerita Vanderbilt University School of Medicine

DISORDERS OF THE MOTOR SYSTEM. Jeanette J. Norden, Ph.D. Professor Emerita Vanderbilt University School of Medicine DISORDERS OF THE MOTOR SYSTEM Jeanette J. Norden, Ph.D. Professor Emerita Vanderbilt University School of Medicine THE MOTOR SYSTEM To understand disorders of the motor system, we need to review how a

More information

Multiple system atrophy

Multiple system atrophy Chapter 3 Roberta Multiple system atrophy Granata and Gregor K. Wenning Abstract Multiple system atrophy (MSA) is a sporadic and rapidly progressive neurodegenerative disorder presenting with autonomic

More information

14 - Central Nervous System. The Brain Taft College Human Physiology

14 - Central Nervous System. The Brain Taft College Human Physiology 14 - Central Nervous System The Brain Taft College Human Physiology Development of the Brain The brain begins as a simple tube, a neural tube. The tube or chamber (ventricle) is filled with cerebrospinal

More information

MOVEMENT OUTLINE. The Control of Movement: Muscles! Motor Reflexes Brain Mechanisms of Movement Mirror Neurons Disorders of Movement

MOVEMENT OUTLINE. The Control of Movement: Muscles! Motor Reflexes Brain Mechanisms of Movement Mirror Neurons Disorders of Movement MOVEMENT 2 Dr. Steinmetz 3 OUTLINE The Control of Movement: Muscles! Motor Reflexes Brain Mechanisms of Movement Mirror Neurons Disorders of Movement Parkinson s Disease Huntington s Disease 1 4 TYPES

More information

Unit 3: The Biological Bases of Behaviour

Unit 3: The Biological Bases of Behaviour Unit 3: The Biological Bases of Behaviour Section 1: Communication in the Nervous System Section 2: Organization in the Nervous System Section 3: Researching the Brain Section 4: The Brain Section 5: Cerebral

More information

BASAL GANGLIA. Dr JAMILA EL MEDANY

BASAL GANGLIA. Dr JAMILA EL MEDANY BASAL GANGLIA Dr JAMILA EL MEDANY OBJECTIVES At the end of the lecture, the student should be able to: Define basal ganglia and enumerate its components. Enumerate parts of Corpus Striatum and their important

More information

Biological Bases of Behavior. 8: Control of Movement

Biological Bases of Behavior. 8: Control of Movement Biological Bases of Behavior 8: Control of Movement m d Skeletal Muscle Movements of our body are accomplished by contraction of the skeletal muscles Flexion: contraction of a flexor muscle draws in a

More information

The Nervous System: Sensory and Motor Tracts of the Spinal Cord

The Nervous System: Sensory and Motor Tracts of the Spinal Cord 15 The Nervous System: Sensory and Motor Tracts of the Spinal Cord PowerPoint Lecture Presentations prepared by Steven Bassett Southeast Community College Lincoln, Nebraska Introduction Millions of sensory

More information

Extrapyramidal Motor System. Basal Ganglia or Striatum. Basal Ganglia or Striatum 3/3/2010

Extrapyramidal Motor System. Basal Ganglia or Striatum. Basal Ganglia or Striatum 3/3/2010 Extrapyramidal Motor System Basal Ganglia or Striatum Descending extrapyramidal paths receive input from other parts of motor system: From the cerebellum From the basal ganglia or corpus striatum Caudate

More information

Human Anatomy. Autonomic Nervous System

Human Anatomy. Autonomic Nervous System Human Anatomy Autonomic Nervous System 1 Autonomic Nervous System ANS complex system of nerves controls involuntary actions. Works with the somatic nervous system (SNS) regulates body organs maintains

More information

Overview. Overview. Parkinson s disease. Secondary Parkinsonism. Parkinsonism: Motor symptoms associated with impairment in basal ganglia circuits

Overview. Overview. Parkinson s disease. Secondary Parkinsonism. Parkinsonism: Motor symptoms associated with impairment in basal ganglia circuits Overview Overview Parkinsonism: Motor symptoms associated with impairment in basal ganglia circuits The differential diagnosis of Parkinson s disease Primary vs. Secondary Parkinsonism Proteinopathies:

More information

A guide to Multiple System Atrophy for: General Practitioners

A guide to Multiple System Atrophy for: General Practitioners Introduction Prevalence Duration Initial presentation Red flags and symptoms Key management problems GP support The MSA Trust A guide to Multiple System Atrophy for: General Practitioners This document

More information

:{ic0fp'16. Geriatric Medicine: Blood Pressure Monitoring in the Elderly. Terrie Ginsberg, DO, FACOI

:{ic0fp'16. Geriatric Medicine: Blood Pressure Monitoring in the Elderly. Terrie Ginsberg, DO, FACOI :{ic0fp'16 ACOFP 53 rd Annual Convention & Scientific Seminars Geriatric Medicine: Blood Pressure Monitoring in the Elderly Terrie Ginsberg, DO, FACOI Blood Pressure Management in the Elderly Terrie B.

More information

Parkinsonism or Parkinson s Disease I. Symptoms: Main disorder of movement. Named after, an English physician who described the then known, in 1817.

Parkinsonism or Parkinson s Disease I. Symptoms: Main disorder of movement. Named after, an English physician who described the then known, in 1817. Parkinsonism or Parkinson s Disease I. Symptoms: Main disorder of movement. Named after, an English physician who described the then known, in 1817. Four (4) hallmark clinical signs: 1) Tremor: (Note -

More information

Evaluation of Parkinson s Patients and Primary Care Providers

Evaluation of Parkinson s Patients and Primary Care Providers Evaluation of Parkinson s Patients and Primary Care Providers 2018 Movement Disorders Half Day Symposium Elise Anderson MD Medical Co-Director, PBSI Movement Disorders 6/28/2018 1 Disclosures GE Speaker,

More information

Transcranial sonography in movement disorders

Transcranial sonography in movement disorders Transcranial sonography in movement disorders Uwe Walter 1st Residential Training of the European Society of Neurosonology and Cerebral Hemodynamics September 7-12, 2008 Bertinoro, Italy Department of

More information

Lecturer. Prof. Dr. Ali K. Al-Shalchy MBChB/ FIBMS/ MRCS/ FRCS 2014

Lecturer. Prof. Dr. Ali K. Al-Shalchy MBChB/ FIBMS/ MRCS/ FRCS 2014 Lecturer Prof. Dr. Ali K. Al-Shalchy MBChB/ FIBMS/ MRCS/ FRCS 2014 Dorsal root: The dorsal root carries both myelinated and unmyelinated afferent fibers to the spinal cord. Posterior gray column: Long

More information

Brainstem. Steven McLoon Department of Neuroscience University of Minnesota

Brainstem. Steven McLoon Department of Neuroscience University of Minnesota Brainstem Steven McLoon Department of Neuroscience University of Minnesota 1 Course News Change in Lab Sequence Week of Oct 2 Lab 5 Week of Oct 9 Lab 4 2 Goal Today Know the regions of the brainstem. Know

More information

Parts of the motor circuits

Parts of the motor circuits MOVEMENT DISORDERS Parts of the motor circuits cortical centers: there are centers in all the cortical lobes subcortical centers: caudate nucleus putamen pallidum subthalamical nucleus (Luys) nucleus ruber

More information

Motor System Hierarchy

Motor System Hierarchy Motor Pathways Lectures Objectives Define the terms upper and lower motor neurons with examples. Describe the corticospinal (pyramidal) tract and the direct motor pathways from the cortex to the trunk

More information

Sleep-Disordered Breathing and Risk of Sudden Death in Multiple System Atrophy

Sleep-Disordered Breathing and Risk of Sudden Death in Multiple System Atrophy Sleep-Disordered Breathing and Risk of Sudden Death in Multiple System Atrophy Lisa Cutchen MD Sleep Medicine Fellow University of New Mexico Sleep Disorders Center New Mexico Thoracic Society February

More information

Basal ganglia Sujata Sofat, class of 2009

Basal ganglia Sujata Sofat, class of 2009 Basal ganglia Sujata Sofat, class of 2009 Basal ganglia Objectives Describe the function of the Basal Ganglia in movement Define the BG components and their locations Describe the motor loop of the BG

More information

I: To describe the pyramidal and extrapyramidal tracts. II: To discuss the functions of the descending tracts.

I: To describe the pyramidal and extrapyramidal tracts. II: To discuss the functions of the descending tracts. Descending Tracts I: To describe the pyramidal and extrapyramidal tracts. II: To discuss the functions of the descending tracts. III: To define the upper and the lower motor neurons. 1. The corticonuclear

More information

Parkinson Disease. Lorraine Kalia, MD, PhD, FRCPC. Presented by: Ontario s Geriatric Steering Committee

Parkinson Disease. Lorraine Kalia, MD, PhD, FRCPC. Presented by: Ontario s Geriatric Steering Committee Parkinson Disease Lorraine Kalia, MD, PhD, FRCPC Key Learnings Parkinson Disease (L. Kalia) Key Learnings Parkinson disease is the most common but not the only cause of parkinsonism Parkinson disease is

More information

The neurvous system senses, interprets, and responds to changes in the environment. Two types of cells makes this possible:

The neurvous system senses, interprets, and responds to changes in the environment. Two types of cells makes this possible: NERVOUS SYSTEM The neurvous system senses, interprets, and responds to changes in the environment. Two types of cells makes this possible: the neuron and the supporting cells ("glial cells"). Neuron Neurons

More information

Basal Ganglia George R. Leichnetz, Ph.D.

Basal Ganglia George R. Leichnetz, Ph.D. Basal Ganglia George R. Leichnetz, Ph.D. OBJECTIVES 1. To understand the brain structures which constitute the basal ganglia, and their interconnections 2. To understand the consequences (clinical manifestations)

More information

Early Clinical Features of Parkinson s Disease and Related Disorders. Dr. Alastair Noyce

Early Clinical Features of Parkinson s Disease and Related Disorders. Dr. Alastair Noyce 1 Specialist Registrar in Neurology, London Deanery Parkinson s UK Doctoral Research Fellow Project lead for PREDICT-PD Declarations Salary: Parkinson's UK, Barts and the London NHS Trust Grants: Parkinson's

More information

CHAPTER 15 LECTURE OUTLINE

CHAPTER 15 LECTURE OUTLINE CHAPTER 15 LECTURE OUTLINE I. INTRODUCTION A. The autonomic nervous system (ANS) regulates the activity of smooth muscle, cardiac muscle, and certain glands. B. Operation of the ANS to maintain homeostasis,

More information

SENSORY (ASCENDING) SPINAL TRACTS

SENSORY (ASCENDING) SPINAL TRACTS SENSORY (ASCENDING) SPINAL TRACTS Dr. Jamila El-Medany Dr. Essam Eldin Salama OBJECTIVES By the end of the lecture, the student will be able to: Define the meaning of a tract. Distinguish between the different

More information

Movement Disorders Will Garrett, M.D Assistant Professor of Neurology

Movement Disorders Will Garrett, M.D Assistant Professor of Neurology Movement Disorders Will Garrett, M.D Assistant Professor of Neurology I. The Basal Ganglia The basal ganglia are composed of several structures including the caudate and putamen (collectively called the

More information

Nsci 2100: Human Neuroanatomy 2017 Examination 3

Nsci 2100: Human Neuroanatomy 2017 Examination 3 Name KEY Lab Section Nsci 2100: Human Neuroanatomy 2017 Examination 3 On this page, write your name and lab section. On your bubble answer sheet, enter your name (last name, space, first name), internet

More information

10/3/2016. T1 Anatomical structures are clearly identified, white matter (which has a high fat content) appears bright.

10/3/2016. T1 Anatomical structures are clearly identified, white matter (which has a high fat content) appears bright. H2O -2 atoms of Hydrogen, 1 of Oxygen Hydrogen just has one single proton and orbited by one single electron Proton has a magnetic moment similar to the earths magnetic pole Also similar to earth in that

More information

The Central Nervous System I. Chapter 12

The Central Nervous System I. Chapter 12 The Central Nervous System I Chapter 12 The Central Nervous System The Brain and Spinal Cord Contained within the Axial Skeleton Brain Regions and Organization Medical Scheme (4 regions) 1. Cerebral Hemispheres

More information

Introduction, use of imaging and current guidelines. John O Brien Professor of Old Age Psychiatry University of Cambridge

Introduction, use of imaging and current guidelines. John O Brien Professor of Old Age Psychiatry University of Cambridge Introduction, use of imaging and current guidelines John O Brien Professor of Old Age Psychiatry University of Cambridge Why do we undertake brain imaging in AD and other dementias? Exclude other causes

More information

Objectives. Distinguishing Parkinson s disease from other parkinsonian and tremor syndromes. Characteristics. Basal Ganglia Structures

Objectives. Distinguishing Parkinson s disease from other parkinsonian and tremor syndromes. Characteristics. Basal Ganglia Structures 12:45 1:30 pm PD or not PD? Distinguishing Parkinson s Disease From Other Parkinsonian and Tremor Syndromes SPEAKER Jennifer G. Goldman, MD, MS Presenter Disclosure Information The following relationships

More information

Premotor PD: autonomic failure

Premotor PD: autonomic failure Premotor PD: autonomic failure Division of Neurobiology Department of Neurology Medical University of Innsbruck Non-motor symptoms in PD Autonomic OH, constipation, impotence, urinary incontinence or retention,

More information

Nervous System. 1. What N.S. division controls skeletal muscles? 3. What kind of neuroglia myelinates axons in the PNS?

Nervous System. 1. What N.S. division controls skeletal muscles? 3. What kind of neuroglia myelinates axons in the PNS? . What N.S. division controls skeletal muscles? Nervous System SRS Review %. Central nervous system %. Peripheral nervous system %. Afferent division %. Somatic division %. Autonomic division %. Sympathetic

More information

Corporate Medical Policy

Corporate Medical Policy Corporate Medical Policy Dopamine Transporter Imaging with Single Photon Emission File Name: Origination: Last CAP Review: Next CAP Review: Last Review: dopamine_transporter_imaging_with_single_photon_emission_computed_tomography

More information

Making Things Happen 2: Motor Disorders

Making Things Happen 2: Motor Disorders Making Things Happen 2: Motor Disorders How Your Brain Works Prof. Jan Schnupp wschnupp@cityu.edu.hk HowYourBrainWorks.net On the Menu in This Lecture In the previous lecture we saw how motor cortex and

More information

Acetylcholine (ACh) Action potential. Agonists. Drugs that enhance the actions of neurotransmitters.

Acetylcholine (ACh) Action potential. Agonists. Drugs that enhance the actions of neurotransmitters. Acetylcholine (ACh) The neurotransmitter responsible for motor control at the junction between nerves and muscles; also involved in mental processes such as learning, memory, sleeping, and dreaming. (See

More information

Ch 13: Central Nervous System Part 1: The Brain p 374

Ch 13: Central Nervous System Part 1: The Brain p 374 Ch 13: Central Nervous System Part 1: The Brain p 374 Discuss the organization of the brain, including the major structures and how they relate to one another! Review the meninges of the spinal cord and

More information

Dizziness, postural hypotension and postural blackouts: Two cases suggesting multiple system atrophy

Dizziness, postural hypotension and postural blackouts: Two cases suggesting multiple system atrophy Dizziness, postural hypotension and postural blackouts: Two cases suggesting multiple system atrophy Dr Rahul Chakor, Associate Prof and Head Dept of Neurology, Dr Anand Soni, Senior Resident, T N Medical

More information

Basal Ganglia. Steven McLoon Department of Neuroscience University of Minnesota

Basal Ganglia. Steven McLoon Department of Neuroscience University of Minnesota Basal Ganglia Steven McLoon Department of Neuroscience University of Minnesota 1 Course News Graduate School Discussion Wednesday, Nov 1, 11:00am MoosT 2-690 with Paul Mermelstein (invite your friends)

More information

Biological Bases of Behavior. 3: Structure of the Nervous System

Biological Bases of Behavior. 3: Structure of the Nervous System Biological Bases of Behavior 3: Structure of the Nervous System Neuroanatomy Terms The neuraxis is an imaginary line drawn through the spinal cord up to the front of the brain Anatomical directions are

More information

Unit VIII Problem 5 Physiology: Cerebellum

Unit VIII Problem 5 Physiology: Cerebellum Unit VIII Problem 5 Physiology: Cerebellum - The word cerebellum means: the small brain. Note that the cerebellum is not completely separated into 2 hemispheres (they are not clearly demarcated) the vermis

More information

Chemical Control of Behavior and Brain 1 of 9

Chemical Control of Behavior and Brain 1 of 9 Chemical Control of Behavior and Brain 1 of 9 I) INTRO A) Nervous system discussed so far 1) Specific 2) Fast B) Other systems extended in space and time 1) Nonspecific 2) Slow C) Three components that

More information

Dr. Farah Nabil Abbas. MBChB, MSc, PhD

Dr. Farah Nabil Abbas. MBChB, MSc, PhD Dr. Farah Nabil Abbas MBChB, MSc, PhD The Basal Ganglia *Functions in association with motor cortex and corticospinal pathways. *Regarded as accessory motor system besides cerebellum. *Receive most of

More information

Parkinson s Disease Initial Clinical and Diagnostic Evaluation. J. Timothy Greenamyre, MD, PhD

Parkinson s Disease Initial Clinical and Diagnostic Evaluation. J. Timothy Greenamyre, MD, PhD Parkinson s Disease Initial Clinical and Diagnostic Evaluation J. Timothy Greenamyre, MD, PhD Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported

More information

Cheyenne 11/28 Neurological Disorders II. Transmissible Spongiform Encephalopathy

Cheyenne 11/28 Neurological Disorders II. Transmissible Spongiform Encephalopathy Cheyenne 11/28 Neurological Disorders II Transmissible Spongiform Encephalopathy -E.g Bovine4 Spongiform Encephalopathy (BSE= mad cow disease), Creutzfeldt-Jakob disease, scrapie (animal only) -Sporadic:

More information

The Brain Worksheet Sections 5-7

The Brain Worksheet Sections 5-7 The Brain Worksheet Sections 5-7 1. neuroglia 2. autonomic nervous system 3. sensory neurons 4. oligodendrocytes 5. ascending tracts 6. descending tracts 7. saltatory propagation 8. continuous propagation

More information

Name: Period: Chapter 2 Reading Guide The Biology of Mind

Name: Period: Chapter 2 Reading Guide The Biology of Mind Name: Period: Chapter 2 Reading Guide The Biology of Mind The Nervous System (pp. 55-58) 1. What are nerves? 2. Complete the diagram below with definitions of each part of the nervous system. Nervous System

More information

Voluntary Movement. Ch. 14: Supplemental Images

Voluntary Movement. Ch. 14: Supplemental Images Voluntary Movement Ch. 14: Supplemental Images Skeletal Motor Unit: The basics Upper motor neuron: Neurons that supply input to lower motor neurons. Lower motor neuron: neuron that innervates muscles,

More information

Multiple system atrophy (MSA) is a sporadic adult-onset

Multiple system atrophy (MSA) is a sporadic adult-onset ORIGINAL RESEARCH E. Matsusue S. Fujii Y. Kanasaki T. Kaminou E. Ohama T. Ogawa Cerebellar Lesions in Multiple System Atrophy: Postmortem MR Imaging Pathologic Correlations BACKGROUND AND PURPOSE: Cerebellar

More information

Basal nuclei, cerebellum and movement

Basal nuclei, cerebellum and movement Basal nuclei, cerebellum and movement MSTN121 - Neurophysiology Session 9 Department of Myotherapy Basal Nuclei (Ganglia) Basal Nuclei (Ganglia) Role: Predict the effects of various actions, then make

More information

Functional Distinctions

Functional Distinctions Functional Distinctions FUNCTION COMPONENT DEFICITS Start Basal Ganglia Spontaneous Movements Move UMN/LMN Cerebral Cortex Brainstem, Spinal cord Roots/peripheral nerves Plan Cerebellum Ataxia Adjust Cerebellum

More information

Chapter 3. Structure and Function of the Nervous System. Copyright (c) Allyn and Bacon 2004

Chapter 3. Structure and Function of the Nervous System. Copyright (c) Allyn and Bacon 2004 Chapter 3 Structure and Function of the Nervous System 1 Basic Features of the Nervous System Neuraxis: An imaginary line drawn through the center of the length of the central nervous system, from the

More information

STRUCTURAL ORGANIZATION OF THE NERVOUS SYSTEM

STRUCTURAL ORGANIZATION OF THE NERVOUS SYSTEM STRUCTURAL ORGANIZATION OF THE NERVOUS SYSTEM STRUCTURAL ORGANIZATION OF THE BRAIN The central nervous system (CNS), consisting of the brain and spinal cord, receives input from sensory neurons and directs

More information

Chapter 9. Nervous System

Chapter 9. Nervous System Chapter 9 Nervous System Central Nervous System (CNS) vs. Peripheral Nervous System(PNS) CNS Brain Spinal cord PNS Peripheral nerves connecting CNS to the body Cranial nerves Spinal nerves Neurons transmit

More information

For more information about how to cite these materials visit

For more information about how to cite these materials visit Author(s): Peter Hitchcock, PH.D., 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Non-commercial Share Alike 3.0 License: http://creativecommons.org/licenses/by-nc-sa/3.0/

More information

Internal Organisation of the Brainstem

Internal Organisation of the Brainstem Internal Organisation of the Brainstem Major tracts and nuclei of the brainstem (Notes) The brainstem is the major pathway for tracts and houses major nuclei, that contain sensory, motor and autonomics

More information

Visualization and simulated animations of pathology and symptoms of Parkinson s disease

Visualization and simulated animations of pathology and symptoms of Parkinson s disease Visualization and simulated animations of pathology and symptoms of Parkinson s disease Prof. Yifan HAN Email: bctycan@ust.hk 1. Introduction 2. Biochemistry of Parkinson s disease 3. Course Design 4.

More information

Autonomic Nervous System

Autonomic Nervous System Autonomic Nervous System Keri Muma Bio 6 Organization of the Nervous System Efferent Division Somatic Nervous System Voluntary control Effector = skeletal muscles Muscles must be excited by a motor neuron

More information

This is a free sample of content from Parkinson's Disease. Click here for more information or to buy the book.

This is a free sample of content from Parkinson's Disease. Click here for more information or to buy the book. A AADC. See Aromatic amino acid decarboxylase AAV. See Adeno-associated virus Acetylcholine (ACh), functional imaging, 174 175 ACh. See Acetylcholine Adaptive immune system central nervous system, 381

More information

Autonomic Nervous System

Autonomic Nervous System Autonomic Nervous System Objectives 1. Describe the CNS components of the ANS 2. Understand the peripheral pathways that connect the ANS with targets in the body. 3. Understand the classes of disorders

More information

Department of Neurology/Division of Anatomical Sciences

Department of Neurology/Division of Anatomical Sciences Spinal Cord I Lecture Outline and Objectives CNS/Head and Neck Sequence TOPIC: FACULTY: THE SPINAL CORD AND SPINAL NERVES, Part I Department of Neurology/Division of Anatomical Sciences LECTURE: Monday,

More information

Parkinson s Disease and other related movement disorders a video guide to diagnosis

Parkinson s Disease and other related movement disorders a video guide to diagnosis Parkinson s Disease and other related movement disorders a video guide to diagnosis Parkinson s Disease Masterclass November 2017 Dr Frank Phelan MidYorkshire Hospitals NHS Trust Ideopathic Parkinson s

More information

Biomedical Technology Research Center 2011 Workshop San Francisco, CA

Biomedical Technology Research Center 2011 Workshop San Francisco, CA Diffusion Tensor Imaging: Parkinson s Disease and Atypical Parkinsonism David E. Vaillancourt court1@uic.edu Associate Professor at UIC Departments t of Kinesiology i and Nutrition, Bioengineering, and

More information

Teach-SHEET Basal Ganglia

Teach-SHEET Basal Ganglia Teach-SHEET Basal Ganglia Purves D, et al. Neuroscience, 5 th Ed., Sinauer Associates, 2012 Common organizational principles Basic Circuits or Loops: Motor loop concerned with learned movements (scaling

More information

Autonomic nervous system

Autonomic nervous system Autonomic nervous system Key notes Autonomic: an independent system that runs on its own The ANS is a visceral and involuntary sensory and motor system The visceral motor fibers in the autonomic nerves

More information