Mv De Angelis

Chronic inflammatory demyelinating polyneuropathy in diabetics: motor conductions are important in the differential diagnosis with diabetic polyneuropathy

OBJECTIVE It is important to recognize CIDP occurring in diabetics because, unlike diabetic polyneuropathy, it is treatable. The aim of this study was to find out whether there are clues which help to differentiate CIDP in diabetics from diabetic polyneuropathy. METHODS We compared the electrophysiological and pathological findings of 7 diabetics, who developed a predominantly motor polyneuropathy with the features of CIDP, with a group of diabetics referred for symptomatic polyneuropathy. RESULTS Of the 7 diabetics we believe developed CIDP, 6 met at least 3 and one patient two of the 4 electrophysiological criteria of demyelination. Of the 100 patients referred for diabetic polyneuropathy, only 4 fulfilled two criteria and none 3. Nerve biopsy findings were not helpful in differential diagnosis, as segmental demyelination and remyelination, onion bulbs and inflammatory infiltrates, which are the histologic features of CIDP, were also present in diabetic polyneuropathy. CONCLUSIONS CIDP can be diagnosed in a diabetic patient when motor symptoms are predominant, are more severe than expected in diabetic polyneuropathy and 3 of the 4 electrophysiological criteria for demyelination are fulfilled. When only two criteria are met, we believe that a trial with one of the established treatments for CIDP may be helpful in confirming the diagnosis.

Dysmyelinating sensory-motor neuropathy in merosin-deficient congenital muscular dystrophy

A 20‐year‐old man with mild myopathy, external ophthalmoparesis, epilepsy, and diffuse white matter hyperintensity in the brain on magnetic resonance imaging had partial merosin deficiency in muscle and absent merosin in the endoneurium. Motor and sensory nerve conduction velocities were slow. Nerve biopsy showed reduction of large myelinated fibers, short internodes, enlarged nodes, excessive variability of myelin thickness, tomacula, and uncompacted myelin, but no evidence of segmental demyelination, naked axons, or onion bulbs. Thus, in congenital muscular dystrophy, merosin expression may be dissociated in different tissues, and the neuropathy is sensory‐motor and due to abnormal myelinogenesis. Muscle Nerve 27: 500–506, 2003

Anti-GD1a antibodies from an acute motor axonal neuropathy patient selectively bind to motor nerve fiber nodes of Ranvier

Acute motor axonal neuropathy (AMAN) is associated with high titer anti-GD1a antibodies. We have found that very high titer IgG anti-GD1a antibodies (Ab) from one AMAN patient selectively bind to motor, but not sensory, nerve nodes of Ranvier. Binding is abolished by preadsorption with GD1a. Sera negative for Ab do not immunostain motor and sensory nerve roots. We have also found that botulinum toxin A (BTA), which binds to GD1a, stains both motor and sensory nerve nodes of Ranvier. Our results strongly support the pathogenetic role of anti-GD1a antibodies in AMAN. Why BTA also binds to sensory fibers still remains to be elucidated, although the different size of BTA and its specificity to other gangliosides present in sensory axons might represent important factors.

Inter-nerves and intra-nerve conduction heterogeneity in CMTX with Arg(15)Gln mutation

OBJECTIVE In X-linked Charcot-Marie-Tooth disease (CMTX), electrophysiological and histopathological studies have suggested either a demyelinating or an axonal polyneuropathy. We report a CMTX family with a striking heterogeneity of nerve conductions between and within nerves. METHODS Two men and one woman have been studied by conduction velocities, sural nerve biopsy with morphometry (one man) and DNA analysis. RESULTS In both men motor conduction velocities were slowed in the demyelinating range, conduction velocity differences among nerves in the same subject varied from 13 to 24 m/s, and distal median compound muscle action potential (CMAP) amplitudes were 3-5 times reduced compared to ulnar CMAPs. Abnormal area reduction or excessive temporal dispersion of proximal CMAP was present in at least two nerves in all patients. Sural nerve biopsy showed reduction of large myelinated fibres, cluster formations, occasional onion bulbs. Teased fibres study revealed short internodes for fibre diameter, enlarged Ranvier nodes but no evidence of segmental demyelination and remyelination. DNA analysis showed an Arg(15)Gln mutation in connexin32 gene in all patients. CONCLUSIONS In this family conduction slowing and segmental conduction abnormalities, in absence of morphological evidence of de-remyelination, may be related to short internodes, widened Ranvier nodes and the specific effect of the mutation. The occurrence in some CMTX patients of a non uniform involvement between and within nerves, as in acquired demyelinating neuropathies, should be kept in mind to avoid misdiagnoses.

Facioscapulohumeral muscular dystrophy presenting isolated monomelic lower limb atrophy. Report of two patients with and without 4q35 rearrangement

Facioscapulohumeral muscular dystrophy has a distinctive regional distribution but variable clinical expression and may be markedly asymmetrical. We report two patients presenting weakness and wasting confined to a single lower limb. Creatine kinase was slightly increased, electromyogram and muscle biopsy were myopathic. Muscle computed tomography showed normal shoulder, mid-arm, pelvic and mid-thigh scans but involvement of calf muscles. In both cases, weakness of facial and periscapular muscles was found in other family members unaware of the disease. Molecular analysis showed 4q35 deletion in one family. These cases broaden the presentation of facioscapulohumeral muscular dystrophy to include isolated monomelic atrophy of lower limb with calf muscle involvement.

Segmental conduction abnormalities and myelin thickenings in Val102/fs null mutation of MPZ gene

The authors report in patients with Val102/fs null mutation a possibly age dependent variability of clinical and electrophysiologic phenotype, segmental conduction abnormalities mainly in ulnar nerves at the elbow, and excessive myelin foldings and thickenings. The authors hypothesize that myelin thickenings at the paranodal region, in concurrence with compression at usual entrapment sites or minor repetitive trauma, may induce segmental conduction abnormalities.

Demyelinating motor Guillain–Barré syndrome following rubella

A 20-year-old man developed weakness without sensory complaints 10 days after rubella. He had fever, typical rubella rash, and suboccipital lymphadenopathy during an epidemic outbreak in his school. Examination showed symmetric weakness of forearm and intrinsic hand muscles, tibioperoneal muscles, and triceps surae (grade 4/5, Medical Research Council scale) and hyperactive tendon reflexes. He could not get up from squatting or walk on heels and toes. Cranial nerves and sensory examination were normal. Serum creatine kinase was normal. Serologic tests revealed immunoglobulin (Ig) G and IgM antirubella. CSF protein content was increased (0.8 g/L). Electrophysiologic examination showed partial motor conduction blocks (CBs) in eight nerves, prolonged distal motor latencies in tibial nerves, and normal sensory conductions even across the sites of CB (figure). EMG of distal muscles of limbs showed reduced recruitment with high frequency discharging motor units. Brain and spinal MRI and median and tibial somatosensory evoked potentials were normal. A diagnosis of Guillain–Barre syndrome (GBS) was made, and the patient was treated with four plasmaphereses with complete recovery in 6 months. On serial electrophysiologic examination, CBs disappeared in 8 to 16 weeks, and abnormal temporal dispersion occurred in four nerves, indicating that demyelination was the pathophysiologic basis (see figure). Sensory conductions remained normal, and fibrillation potentials were not detected through …

Myelin thickenings in val 102/fs null mutation of MPZ gene

Myelin thickenings, abnormal myelin foldings and tomacula have been rarely described in CMT1B. In two unrelated patients of different age (patient 1: 29 years old; patient 2: 65 years old) with CMT1B and Val 102/fs null mutation of MPZ gene we performed morphometric analysis, teased fibers and ultrastructural examination of sural nerve. We found: 1) markedly decreased fiber density with prevalent loss of large diameter fibers (patient 1: 4419 fibers/mm2; patient 2: 1326 fibers/mm2); 2) evidence of de‐remyelination; and 3) paranodal and internodal myelin thickenings in virtually all fibers. Patient 1 has myelin thickenings measuring more than 50% of the fiber diameter in 14% of fibers and thickenings greater than 30% in 33% of fibers. Patients 2 presents myelin thickenings measuring more than 50% of fiber diameter in 23% of fibers and thickening greater than 30% in 49% of fibers. When considering the absolute measure of myelin thickenings and their number over 100 internodes, patient 1 presents 150 small myelin thickenings (<8 mm of diameter) whereas patient 2 has 57. The number of globules (8–12 mm of diameter) is 56 in patient 1 and 45 in patient 2. The number of myelin thickenings greater than 12 mm is 33 in patient 1 and 45 in patient 2. Ultrathin sections showed myelin infoldings, outfoldings and uncompacted myelin. CMT1B with a heterozygous null mutation of MPZ gene is characterized by abundant focal myelin thickenings. Similar findings have been described in the P0 deficient heterozygous mice.

Demyelinating motor guillain-barré syndrome following rubella

A 20‐year‐old man developed weakness without sensory complaints ten days after rubella. Examination showed limb weakness and brisk tendon reflexes but no sensory abnormalities. Laboratory investigations revealed IgG and IgM anti‐Rubella and increased CSF protein content (0,8 g/L). Electrophysiological examination showed partial motor conduction blocks in eight nerves and normal sensory conductions even across the sites of CB. Brain and spinal cord MRI and SEPs were normal. The patient was treated with four plasmaphereses and fully recovered in six months. Conduction blocks gradually improved with increasing duration and abnormal temporal dispersion in proximal CMAPs. GBS has been rarely reported after rubella. Anti‐myelin basic protein antibodies have been found in a patient with a relapsing motor neuropathy following rubella vaccination. As antibodies cross‐reacted with a viral protein, molecular mimicry has been proposed as a pathophysiological mechanism. In our patient we did not find anti‐MBP antibodies and antibodies to‐glycolipids (GM1, GM2, GA1, GD1a, GD1b, GQ1b, sulfatides, galactocerebroside) were also negative. Indirect immunofluorescence after incubation of patients serum on rabbit sciatic nerve and human sural nerve and roots was negative. Our patient confirms the occurrence of GBS following Rubella and shows some uncommon features: 1) hyperactive deep tendon reflexes; 2) demyelination selectively involving motor fibres; and 3) widespread early conduction blocks in intermediate nerve segments.