From Head to Toe
Katherine Keller, DO Internal Medicine Resident, Maine Medical Center
Maine ACP Annual Meeting Clinical Vignette- September 16, 2017
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
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
Emergency Room #2:
● One week later brought to ED after being found confused and lethargic
● At this point patient is admitted
Past Medical History
Heterozygote for Factor V Leiden No personal history of venous thromboembolism
Medications
Hydrochlorothiazide
Medroxyprogesterone contraceptive injection
Family History
Factor V Leiden (Mother)
Deep venous thrombosis (Mother)
Social History
-Lives with her husband
-Works as a nurse
-Current everyday smoker
-Drinks alcohol occasionally
-Denies illicit drug use
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
Outside hospital Course
Admitted with encephalopathy and seizure EEG: Mildy slow background, no definite epileptiform activity CT head: Suspicious dense lesion in occipital lobe
Outside Hospital Course
Fig 1. MRI brain without contrast Bilateral cerebral watershed distribution subcortical edematous changes in occipital lobes
Outside Hospital Course
Assessment: ● Posterior Reversible Encephalopathy Syndrome (PRES)
Plan: ● Neurology consult ● Loaded with levetiracetam
● Started on oral antihypertensives
Outside Hospital Course
● Two days later develops right side visual field deficit
Outside Hospital Course
Fig 2. MRI brain without contrast Left occipital lobe infarction
……….Transfer to Maine Medical Center
http://dreamstop.com/wp-content/uploads/2016/09/ambulance-dream.jpg
What do we have on her problem list?
Problem list:
● Recent progestin contraceptive injection
● Abdominal Pain
● Seizure
● Posterior reversible encephalopathy syndrome (PRES)
● Ischemic Stroke
● Hypertension
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
Objective
Labs:
138 104 8
3.9 20 0.57
16.3
13.7
202 7.3
99
Imaging
● Repeat MRI shows multiple cerebral watershed infarctions
● CTV head showed dural venous sinus thrombosis
Imaging
Fig. 3 MRI brain without contrast Multiple watershed zone cerebral infarctions
Imaging
Fig 4. CTA head and neck Diffuse narrowing of posterior and anterior cerebral arteries
Fig 5. CTA head and neck Normal
Imaging
Fig 6. CTA head and neck Diffuse narrowing of posterior and anterior cerebral arteries
Fig 7. CTA head and neck Normal
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
Why does this previously healthy 28 year old have reversible cerebral vasoconstriction syndrome?
What would you do next?
Reversible Cerebral Vasoconstriction Syndrome (RCVS)
Infectious disease:
HIV- negative
CSF studies- unremarkable
Vasculitides:
ANCA- negative
ESR- normal
CRP- normal
Autoimmune:
DS DNA -negative
ANA- negative
ESR- normal
CRP- normal
Medications/toxins:
Oral contraceptive pills
Triptans
Serotonergic antidepresseants
Marijuana
Cocaine
Problem list:
● Abdominal Pain
● Seizure ● Posterior reversible encephalopathy syndrome (PRES)
● Ischemic Stroke
● Hypertension
● Dural Venous Thrombosis
Problem list:
● Abdominal pain
● Seizure ● Posterior reversible encephalopathy syndrome (PRES)
● Ischemic stroke
● Hypertension
● Dural venous thrombosis
● Reversible cerebral vasoconstriction syndrome (RCVS)
Assessment and Plan
● Dural Venous Thrombosis
○ Secondary to hypercoagulable state and recent
progesterone injection
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
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?
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
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
What about the abdominal pain?
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.
https://www.maryvancenc.com/wp-content/uploads/2009/10/period_pain.jpg
MMC Hospital Course #2
Fig 5. CTA head and neck Normal
Fig 7. CTA head and neck Normal
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
Seizure
Peripheral Neuropathy
Abdominal Pain
Encephalopathy
What is going on?
MMC Hospital Course #2
Urine Porphobilinogen
349.5 (normal =< 1.3)
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.
Overview
Discussion: Acute Intermittent Porphyria
Katherine Keller, DO Internal Medicine Resident, Maine Medical Center
Maine ACP Annual Meeting Clinical Vignette- September 16, 2017
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
https://upload.wikimedia.org/wikipedia/commons/thumb/a/a8 /Urine_of_patient_with_porphyria.png/280px-Urine_of_patient_with_porphyria.png
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
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
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
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
Exacerbating Factors
● alcohol
● tobacco
● change in sex hormones, mainly progesterone
● medications, antipsychotics and antiepileptics are main ones
● starvation
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
Treatment ● Our patient was treated with hemin which is standard
treatment of moderate to severe attack
Treatment ● Hemin reduces synthesis of ALAS which decreases accumulation of heme
precursors
● Carbohydrate loading is treatment option for mild attack
Questions?
Thank you: Dr. Stephen Hayes
Dr. John Paul Winters
Dr. Dave Sedar
Dr. Brian Perry
Dr. Mark Gorman
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 1986. P. 35.
3. Kauppinen R, Mustajoki P. Prognosis of acute porphyria: occurence of acute attacks, precipitating factors, and associated disease. Medicine, Balitmore 1992. 71(1):1.
4. Meyer UA, Schuurmans MM, Lindberg RL. Acute porphyria: pathogenesis of neurological manifestations. Semin Liver Dis. 1998. 18(1):43.
5. 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. 56. 713-717. 10.2169/internalmedicine.56.7654.
6. 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
Top Related