Katherine Keller, DO Internal Medicine Resident, Maine Medical Center Maine ACP Annual Meeting Clinical Vignette- September 16, 2017

Transcription

1 From Head to Toe Katherine Keller, DO Internal Medicine Resident, Maine Medical Center Maine ACP Annual Meeting Clinical Vignette- September 16, 2017

2 Initial presentation to PCP 28 year old healthy female presents with: abdominal pain for 3 weeks nausea/vomiting notes hormonal intrauterine device removed and had medroxyprogesterone injection 1 week prior to symptoms

3 Emergency Room Presents to emergency room the next day with diffuse abdominal pain and burning pain in bilateral flanks Abdominal CT normal besides questionable sludge in gallbladder Noted to be hypertensive Given ondansetron and analgesics Started on hydrochlorothiazide for hypertension

4 Emergency Room #2: One week later brought to ED after being found confused and lethargic At this point patient is admitted

5 Past Medical History Heterozygote for Factor V Leiden No personal history of venous thromboembolism

6 Medications Hydrochlorothiazide Medroxyprogesterone contraceptive injection

7 Family History Factor V Leiden (Mother) Deep venous thrombosis (Mother)

8 Social History -Lives with her husband -Works as a nurse -Current everyday smoker -Drinks alcohol occasionally -Denies illicit drug use

9 Outside Hospital Course Vital Signs: BP 170/132 HR 134 RR 9 T 36.7 SpO2 100% RA Labs: Na-125 K- 2.4 HCG- negative Physical Exam: Noted to have generalized tonic clonic seizure while in ED Non focal exam Cardiopulmonary within normal limits

10 Outside hospital Course Admitted with encephalopathy and seizure EEG: Mildy slow background, no definite epileptiform activity CT head: Suspicious dense lesion in occipital lobe

11 Outside Hospital Course Fig 1. MRI brain without contrast Bilateral cerebral watershed distribution subcortical edematous changes in occipital lobes

12 Outside Hospital Course Assessment: Posterior Reversible Encephalopathy Syndrome (PRES) Plan: Neurology consult Loaded with levetiracetam Started on oral antihypertensives

13 Outside Hospital Course Two days later develops right side visual field deficit

14 Outside Hospital Course Fig 2. MRI brain without contrast Left occipital lobe infarction

15 to Maine Medical Center

16 What do we have on her problem list?

17 Problem list: Abdominal Pain Seizure Hypertension Posterior reversible encephalopathy syndrome (PRES) Ischemic Stroke Recent progestin contraceptive injection

18 Objective Vital Signs: BP 123/ 83 P 99 T 36.9 RR 15 SpO2 98% BMI 21 Physical Exam: General: Somnolent and flat affect, delayed responses. HEENT: PERRLA, EOMI intact bilaterally. Moist mucosa. CV: Regular rate and rhythm. No murmur. Respiratory: Clear to auscultation bilaterally Abdomen: Soft, non tender, non distended Extremities: No lower extremity edema Skin: No rashes Neuro: CN: 2-12 intact, subtle right lateral visual field deficit Motor: Strength 5/5 throughout bilaterally Sensation: Intact throughout Tone: Normal

19 Objective Labs:

20 Imaging Repeat MRI shows multiple cerebral watershed infarctions CTV head showed dural venous sinus thrombosis

21 Imaging Fig. 3 MRI brain without contrast Multiple watershed zone cerebral infarctions

22 Imaging Fig 4. CTA head and neck Diffuse narrowing of posterior and anterior cerebral arteries Fig 5. CTA head and neck Normal

23 Imaging Fig 6. CTA head and neck Diffuse narrowing of posterior and anterior cerebral arteries Fig 7. CTA head and neck Normal

24 MMC Hospital Course Diffuse cerebral artery narrowing Concern for reversible cerebral vasoconstriction syndrome (RCVS) Cerebral angiogram with neurosurgery revealed diffuse vasospasm consistent with RCVS Character of vessels did not appear to be consistent vasculitis

25 Why does this previously healthy 28 year old have reversible cerebral vasoconstriction syndrome? What would you do next?

26 Reversible Cerebral Vasoconstriction Syndrome (RCVS) Infectious disease: HIV- negative CSF studies- unremarkable Autoimmune: DS DNA -negative ANA- negative Vasculitides: ANCA- negative ESR- normal CRP- normal ESR- normal CRP- normal Medications/toxins: Oral contraceptive pills Triptans Serotonergic antidepresseants Marijuana Cocaine

27 Problem list: Abdominal Pain Seizure Posterior reversible encephalopathy syndrome (PRES) Ischemic Stroke Hypertension Dural Venous Thrombosis

28 Problem list: Abdominal pain Seizure Posterior reversible encephalopathy syndrome (PRES) Ischemic stroke Hypertension Dural venous thrombosis Reversible cerebral vasoconstriction syndrome (RCVS)

29 Assessment and Plan Dural Venous Thrombosis Secondary to hypercoagulable state and recent progesterone injection

30 Assessment and Plan Dural Venous Thrombosis Secondary to hypercoagulable state and recent progesterone injection Ischemic stroke Secondary to rapid blood pressure lowering in the setting of PRES which was likely RCVS initially

31 Assessment and Plan Dural Venous Thrombosis Secondary to hypercoagulable state and recent progesterone injection Ischemic stroke Secondary to rapid blood pressure lowering in the setting of PRES which was likely RCVS initially PRES Was this ever just PRES?

32 Assessment and Plan Dural Venous Thrombosis Secondary to hypercoagulable state and recent progesterone injection Ischemic stroke Secondary to rapid blood pressure lowering in the setting of PRES which was likely RCVS initially PRES Was this ever just PRES? RCVS Secondary to recent progesterone injection All other work-up was negative

33 MMC Hospital Course Treatment: Calcium channel blocker, amlodipine, for vasospasm Analgesics and gabapentin for headache Dabigatran initiated for dural venous thrombosis Discharged to inpatient rehab

34 What about the abdominal pain?

35 MMC Hospitalization #2 Patient returns 2 days after being discharge to inpatient rehab with Headache, abdominal pain, nausea, vomiting, and burning pain all over her body.

36 MMC Hospital Course #2 Fig 7. CTA head and neck Normal Fig 5. CTA head and neck Normal

37 MMC Hospital Course #2 Repeat inflammatory markers normal Patient continues to have all over body pain despite increasing gabapentin and oxycodone Writhes around in pain in her dimly lit room with very flat affect Questioned conversion disorder or situational anxiety disorder

38 Abdominal Pain Seizure What is going on? Peripheral Neuropathy Encephalopathy

39 MMC Hospital Course #2 Urine Porphobilinogen (normal =< 1.3)

40 Acute Porphyria Diagnosis: Substantial elevations of urinary porphobilinogen, greater than 10, is sufficient for diagnosis of acute porphyria. Treatment should be started immediately without waiting for additional testing.

41 Overview

42 Discussion: Acute Intermittent Porphyria Katherine Keller, DO Internal Medicine Resident, Maine Medical Center Maine ACP Annual Meeting Clinical Vignette- September 16, 2017

43 History Porphyrin and porphyria (identified in urine in 1871) are derived from the Greek word porphyrus, which mean purple. Urine may be reddish in color due to the presence of excess porphyrins and the urine may darken after exposure to light.y /Urine_of_patient_with_porphyria.png/280px-Urine_of_patient_with_porphyria.png

44 Epidemiology Inherited, autosomal dominant gene but low penetrance Incidence 5 : 100,000 More likely to manifest in women More common in individual of northern european descent Onset usually age 30-50

45 Pathophysiology Disorder in the production of heme due to faulty enzyme porphobilinogen deaminase (PBGD) Mutations in porphobilinogen deaminase (PBGD) gene lead to reduced function Few with mutation will have symptomatic disease; many individuals with mutation in this gene will remain asymptomatic

46 Pathophysiology Accumulation of porphobilinogen in the cytoplasm Aminolevulinic acid synthase (ALAS) induction in liver leads to heme synthesis and activity of PBGD Metabolic stress, drugs, and restriction of carbohydrates lead to increases in ALAS

47 Clinical Manifestations Abdominal pain Peripheral neuropathy Lower extremity pain Paresthesias Central nervous system involvement Seizure Hypothalamic involvement can cause SIADH MRI findings consistent with posterior reversible encephalopathy syndrome (PRES) Neuropsychiatric Neuropathic bladder dysfunction Red/dark urine

48 Exacerbating Factors alcohol tobacco change in sex hormones, mainly progesterone medications, antipsychotics and antiepileptics are main ones starvation

49 Encephalopathy and Acute Intermittent Porphyria Case reports of both PRES and RCVS have been seen in presentation of acute intermittent porphyria Exact pathophysiology of each is not well known or studied Clinically significant because the treatment of each is different Rapid lowering of blood pressure can leading to infarction as seen in our patient Prolonged vasoconstriction can cause ischemia in watershed areas as we saw in our patient

50 Treatment Our patient was treated with hemin which is standard treatment of moderate to severe attack

51 Treatment Hemin reduces synthesis of ALAS which decreases accumulation of heme precursors Carbohydrate loading is treatment option for mild attack

52 Questions?

53 Thank you: Dr. Stephen Hayes Dr. John Paul Winters Dr. Dave Sedar Dr. Brian Perry Dr. Mark Gorman

54

55 References: 1. Sood, Gagan MD, Anderson, Karl MD, Tirnauer, Jennifer MD. (2017) Pathogenesis, clinical manifestation, and diagnosis of acute intermittent porphyria. Uptodate. 2. Grandchamp B, Beaumont C, deverneuil H, et al. Genetic Expression of porphobilinogen deaminase and urod during the erythroid differentiation of mouse erythroleukemic cells. In: Porphyrins and porphyrias, Nordmann Y (Ed), John Libbey and company, London P Kauppinen R, Mustajoki P. Prognosis of acute porphyria: occurence of acute attacks, precipitating factors, and associated disease. Medicine, Balitmore (1):1. 4. Meyer UA, Schuurmans MM, Lindberg RL. Acute porphyria: pathogenesis of neurological manifestations. Semin Liver Dis (1): Takata, Tadayuki & Kume, Kodai & Kokudo, Yohei & Ikeda, Kazuyo & Kamada, Masaki & Touge, Tetsuo & Deguchi, Kazushi & Masaki, Tsutomu. (2017). Acute Intermittent Porphyria Presenting with Posterior Reversible Encephalopathy Syndrome, Accompanied by Prolonged Vasoconstriction. Internal Medicine /internalmedicine Soo Y, Singhal AB, Leung T, Yu S, Mak H, Hao Q, Leung H, Lam W, Wong LK. Reversible cerebral vasoconstriction syndrome with posterior leucoencephalopathy after oral contraceptive pills. Cephalgia. 2010; 30(1):42