FAMILIAL TOMACULOUS NEUROPATHY

FAMILIAL TOMACULOUS NEUROPATHY

Harish S Hosalkar, Karl Dalal, Hetal Shah, Priti S Gujar
*Orthopaedic Surgeon; **Resident, Paediatrics; ***Anaesthesiologist; ****Radiologist, Bai Jerbai Wadia Hospital for Children, Mumbai.

INTRODUCTION

Hereditary neuropathy with liability to recurrent pressure - sensitive palsies (also called tomaculous neuropathy) is an autosomal dominant disorder that produces an episodic, recurrent demyelinating neuropathy. Isolated peripheral nerve palsies are fairly common and are usually due to trauma or associated disease. Recurrent peripheral nerve palsies are rare especially the familial variants are extremely rare.

In the family reported here there were multiple entrapment neuropathies in the presenting patient (five-year female child) as well as two preceding generations. The interesting features of the case are presented.

The patient, a 5 year old female Indian child, born of a non consanguineous marriage presented to the out patient department with insidious onset numbness in her right little finger and the ulnar side of her right finger. She felt that these fingers were weak especially when she tried to grip anything. Rest of the limb was unaffected and she had neither paraesthesiae nor pain. X-rays of the hand were taken. Thorough clinical examination revealed no positive findings. The child was given oral anti-inflammatory agents and recovered completely within the next 3 days. Three weeks later the finger suddenly became weak and numb again, and the same evening, when the child had been kneeling for about 10 minutes she began dragging her foot and could not dorsiflex it. She had no paraesthesiae, pain or numbness and the leg recovered the next evening. The child had no other illness and past history was not contributory. On examination there was no sensory loss. Reflexes were normal and equal and characteristic ulnar claw was evident.

Interestingly, both parents complained of tingling and grip weakness occasionally, in their right hands. Hence nerve conduction studies were also performed on both the mother and father. Both showed evidence of a median entrapment neuropathy, unilaterally, suggesting carpal tunnel syndrome. Detailed history of all first-degree relatives revealed adolescent onset neuropathy in maternal grandfather.

1. Distal latencies were markedly prolonged in the right median nerve. Other distal latencies were more or less normal.

2. Cmap amplitudes were normal in all nerves examined. However there was some conduction block noted in the left ulnar nerve. There was a severe conduction block in the right ulnar nerve with a drop in amplitude across at the cubital tunnel.

3. Motor nerve conduction was mildly reduced in the median nerves bilaterally. The right ulnar nerve showed marked reduction of conduction velocity across the cubital tunnel.

4. ‘F’ waves were absent in the ulnar nerves and were normal in the tibial nerves in the lower limbs.

5. The SNAP’s appeared to be mildly prolonged on the left side. On the right side they appeared to be normal.

6. Concentration needle EMG revealed chronic partial denervation with only a single motor unit in the right FDI suggesting significant denervation.

Biopsy of a sural nerve was performed in and showed typical images of myelin degeneration at various stages, corresponding to the formation of tomacular thickenings or “sausage-like” formations. Although there was a distinctive pathological pattern of myelin thickenings in a high proportion of internodes there was no specific pattern of myelin thickening in a high proportion of internodes there was no specific pattern of nerve degeneration.

Based on the history, clinical presentation, electrophysiological features and histological findings a diagnosis of autosomal dominant tomaculous neuropathy was made.

Do Jong first described Tomaculous neuropathy in 1947, presenting a family in which 1 man and 4 women in 3 generations had recurrent peroneal neuropathy after digging potatoes in a kneeling position. Davies in 1954 and Earl et al in 1965 have also reported families.[1] The latter group found that motor nerve conduction velocity was reduced in some clinically normal family members. Staal et al in 1965 reported a family in which members in 4 generations showed transient unilateral peroneal palsies. The neuropathy manifested itself especially after prolonged work in a kneeling position.[2] The family, living in Holland, knew the disease as ‘bulb diggers’ palsy. Other nerve palsies, such as ulnar, occur as well.[1] Roos and Thygesen observed 19 cases in 5 generations and reported that the usual age of onset was between 15 and 20 years.[3] The course of the disorder and the episodic nature of the neuropathy, which often was of mechanical provocation, suggested that it was the same disorder as that reported by Davies 1954, Wahle and Tonnis 1958, Earl et al 1964, and others.[3] Guillozet and Mercer in 1973 described 4 cases of recurrent neuropathy in 3 generations of a family. These patients showed recurrent attacks of pain, weakness and sometimes muscle-wasting in the arms and hands. These attacks generally were known to remit gradually, sometimes leaving residual weakness or muscular atrophy. The lower cranial nerves and the sympathetic nervous system may also be affected in some cases.[4]

Histopathology is distinguished by, the presence of sausage-shaped swellings of the myelin sheath, from which the term tomaculous neuropathy (Latin : tomaculum = sausage) was derived.[4] Segmental demyelination is the major change correlating with the episodes of nerve palsy and axonal degeneration might be rarely associated. The myelin sausages are markers of a selective vulnerability of the nerve fibers either to mechanical injury or to some other unknown event.[6]

Oda et al demonstrated that the tomacula occur not only in sensory nerves but also in motor nerves.5 Roos and Thygesen, proposed that X-linked dominant inheritance could not be excluded, however autosomal dominant inheritance was proved by the reports of Davis 1954, Lhermitte et al 1973, Cruz Martinez et al 1977, Dubi et al 1979, and Hinault et al 1981. Subclinical electrophysiologic abnormalities permit demonstration of autosomal dominant inheritance (Staal et al 1965, Debruyne et al 1980). Sellman and Mayer (1987) reported conduction block in 5 nerves of 4 patients from 2 families with hereditary neuropathy.[5] Barisic et al described this disorder in monozygotic twin sisters and their father. Sural nerve biopsy showed “sausage-like” formations. Cortisone was thought to be beneficial.[5]

Martinelli et al described a family in which multiple members had intermittent brachial plexus palsy with the histologic findings of tomaculous neuropathy. Patients showed reduced interpupillary distance (hypotelorism), a finding that has been reported in neuritis with brachial predilection.[5]

The sensory nerve reveals predominantly demyelinating alterations, with focal thickenings of myelin fibres called tomaculi showing numerous subperineural structures termed Renaut Bodies. The EMG findings show a slowing of the nerve conduction velocities and an increase of distal latencies. Hereditary neuropathy generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers.[6]

Our case had evidence of mononeuritis multiplex involving the median and ulnar nerves. There were also entrapment neuropathies at the carpal tunnel and other at the cubital tunnel. Nerve conduction studies performed in both patients showed evidence of median entrapment neuropathy suggesting carpal tunnel syndrome. Autosomal dominant nature of the condition is revealed by similar findings in maternal grandparent. Neuropathy in the father may be purely incidental. EMG and histopathology findings conclude a diagnosis of tomaculous neuropathy.

Dr. MG Yagnik : HOD Orthopaedics; Dr. AR Bacha : Consultant Orthopaedics; Dr. AN Johari : Consultant Orthopaedics; Dean Dr. RH Merchant for permitting to carry out this analysis and presentation.

REFERENCES