Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy.
BACKGROUND
Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE) have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.


METHODS
Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.


RESULTS
Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females) and 17 controls (37.9±9.0 years; 8 females) demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1), L5 radiculopathic sensory impairment (n = 1) and cervical myelopathy (n = 1). In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002) ([95% CI], p-value)) and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089)) in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232)) and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169)).


CONCLUSIONS
We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.
Department of Neurosciences, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, United Kingdom.
Alessia
A
Nicotra
Thalidomide Trust, 1 Eaton Court Road, Colmworth Business Park, Eaton Socon, St Neots, Cambridgeshire, PE19 8ER, United Kingdom.
Claus
C
Newman
Thalidomide Trust, 1 Eaton Court Road, Colmworth Business Park, Eaton Socon, St Neots, Cambridgeshire, PE19 8ER, United Kingdom.
Martin
M
Johnson
United Lincolnshire Hospitals NHS Trust, Lincoln County Hospital, Greetwell Road, Lincoln, LN2 5QY, United Kingdom.
Oleg
O
Eremin
Department of Medical Statistics, University Medical Center Göttingen, 37073, Göttingen, Germany.
Tim
T
Friede
Department of Neurosciences, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, United Kingdom.
Omar
O
Malik
Department of Neurosciences, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, United Kingdom.|Department of Medicine, Division of Experimental Medicine, Centre for Neuroscience, Wolfson Neuroscience Laboratories, Imperial College London, London, United Kingdom.
Richard
R
Nicholas
D000015:Abnormalities, Multiple / Q000139:chemically induced* / Q000503:physiopathology; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000502:physiology; D010525:Peripheral Nerves / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*; D013792:Thalidomide / Q000009:adverse effects*
D013792:Thalidomide