Brainstem

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Complex Labile Hypertension:
A Life On Hold
Ng FL, Lobo MD
Department of Clinical Pharmacology
The William Harvey Research Institute
Barts and The London School of Medicine
BHS Annual Scientific Meeting
14th September 2011
Referral from University Hospital
Galway
• Mr JK, 48 year old male, Construction Worker
• Frequent paroxysms of flushing
• Uncontrolled hypertension for 14 months
– Minute-to-minute lability on intra-arterial monitoring
– Surges on standing, activity and alerting factors
• Collapses postulated secondary to hypotension
Admission to Royal London
• Worsening symptoms over preceding two years
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Flushing, sweating with nausea
Palpitations
Paraesthesia of fingertips
Severe headaches
Early morning epistaxis
Collapses
Erectile dysfunction
Nocturia
Sensations of heat in the body
Lethargy
Additional history
• Other Past Medical History
– Pneumonia aged 33
• Current Medications
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Clonidine
Prazosin
Metoprolol
No drug intolerances
450 micrograms tds
1mg bd
75mg tds
• Ex-smoker
• Nil EtOH since on medications
• No recreational drugs or over the counter medications
Examination
Supine
Standing
BP (mmHg)
141/65
166/97
Pulse (bpm)
70
104
• BMI 28.4 kg/m2
• Absent left radial pulse with previous arterial line
• Otherwise unremarkable
Initial management plan
• Initially withhold medication
• Bed rest and non-invasive monitoring
• Specialist investigations:
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Autonomic testing
Autoimmune profile and anti-neuronal auto-antibodies
Urinary metanephrines and plasma catecholamines
MRI brainstem
Whole body PET FDG Scan
Autonomic Testing
Sympathetic
Deep target organ sympathetic failure
Postganglionic sympathetic failure
Normal muscle and cardioaccelerator
function
Parasympathetic Minimal resting cardiac vagal tone
Attenuated carotid massage response
Baroreflex
Cutaneous
Peripheral baroreflex failure
Partial thermoregulatory failure
Brainstem
Marked abnormal spontaneous activity
Autoimmune profile
• ANA
Anti-Scl-70
Positive
1/640, speckled pattern
Positive
• Anti-Jo-1
Anti-RNP
Anti-Sm
Anti-Ro
Anti-La
Anti-ds DNA
Negative
Negative
Negative
Weak positive
Negative
Negative
• Anti-neuronal antibodies
Negative
Further investigations
• Clinical Neurophysiology
– No abnormalities
• MRI Brainstem
– No evidence of brainstem abnormalities
• Positron Emission Tomography
– No evidence of malignancies
• Skin punch biopsy histology
– No evidence of small fibre neuropathy
Summary
• 48 year old gentleman with
– Progressive symptoms associated with paroxysmal
hypertension, symptomatic hypotension and
autonomic dysfunction
– Testing confirming widespread autonomic dysfunction
– Autoimmune profile suggestive of scleroderma/UCTD
• Diagnoses
– Extreme blood pressure lability due to dysautonomia
– Autoimmune small fibre neuropathy secondary to
underlying scleroderma/UCTD
Management
• BP control and stability achieved through strict bedrest
• Diazepam was initiated to attenuate alerting responses
• Methyldopa and clonidine patches improved symptoms
• Discharged with:
– Clonidine patch
– Methyldopa
– Diazepam
100 micrograms/day
1g at 08:00, 1g at 16:00, 500mg at 20:00
5mg at 09:00, 5mg at 14:00, 3mg at 22:00
Commentary...
Results of autonomic testing...
• Parasympathetic function reduced
• Generalised failure of Sympathetic function to deep and
cutaneous targets
• Denervation Hypersensitivity to phenylephrine
• Poor BP stability during orthostasis (SBP varied by 112
mm Hg)
• However: normal resting supine BP (MAP 92.4 mm Hg)
and normal muscle sympathetic tone during isometric
exercise
What do the tests mean?
• The patient is not hypertensive per se but has very poor
BP stability
• The responsible neurons are small, thinly myelinated or
unmyelinated fibres
• No evidence of large fibre peripheral neuropathy
Further plans
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Repeat skin punch biopsy of Left leg
Thermal Threshold testing
Nail fold capillaroscopy
Rheumatology review
• Adjustment of antihypertensive medications to better
control BP surges
• Consideration of IV γ-globulin therapy to arrest immunemediated neuropathy