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Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families from Bulgaria, has been mapped to 8q24. Further refined mapping of the region has been undertaken on DNA from patients diagnosed across Europe. The refined map consists of 25 microsatellite markers over approximately 3 cM. In this collaborative study we have identified a number of historical recombinations resulting from the spread of the hereditary motor and sensory neuropathy type Lom gene through Europe with the migration and isolation of Gypsy groups. Recombination mapping and the minimal region of homozygosity reduced the original 3 cM hereditary motor and sensory neuropathy type Lom region to a critical interval of about 200 kb.

UNLABELLED: The aim of this work was to assess the hearing impairment in patients with hereditary motor and sensory neuropathy (HMSN). Elevation of pure tone thresholds in the presence of preserved inner ear function as suggested by cochlear microphonics (CM), absent or markedly abnormal brainstem auditory evoked potentials (BAEP), and elevation of speech perception out of proportion to the pure tone loss were found in the patients. From 28 members of a Gypsy family, we examined two siblings aged 31 and 30 years and their nephew aged 20 years, all suffering from HMSN that was associated with auditory neuropathy. All three affected members with difficulty of understanding speech had following investigations: pure tone and speech audiograms, BAEP, cochlear microphonics, and nerve conduction studies (NCV). RESULTS: the older two siblings had a flat 80 dB audiogram, whereas the younger one has flat 20 dB audiogram on the Lt. ear and 30 dB audiogram on the Rt. ear. All had no speech comprehension and no BAEP. Two patients had preserved cochlear microphonics on one ear. Peripheral nerves were electrically not elicitable, however, at the beginning of the disease nerve conduction was slow. CONCLUSION: in all three affected members with distinct clinical picture of HMSN their hearing impairment was proved to be due to severe auditory neuropathy in the presence of preserved inner ear function.

Members of a Roma (Gypsy) family with hereditary motor and sensory peripheral neuropathy (HMSN) and concomitant auditory and vestibular cranial neuropathies were identified in Kocevje, Slovenia. The illness begins in childhood with a severe and progressive motor disability and the deafness is delayed until the second decade. There are no symptoms of vestibular dysfunction. The family structure is consistent with an autosomal recessive pattern of inheritance and the genetic locus for the disorder is linked to the same region of chromosome 8q24 as other Roma families with HMSN and deafness from Lom, Bulgaria (HMSN-Lom). The present study shows that the deafness is caused by a neuropathy of the auditory nerve with preserved measures of cochlear outer hair cell function (otoacoustic emissions and cochlear microphonics) but absent neural components of auditory brainstem potentials. The hearing loss affects speech comprehension out of proportion to the pure tone loss. Vestibular testing showed absence of caloric responses. Physiological and neuropathological studies of peripheral nerves were compatible with the nerve disorder contemporaneously affecting Schwann cells and axons resulting in both slowed nerve conduction and axonal loss. Genetic linkage studies suggest a refinement of the 8q24 critical region containing the HMSN-Lom locus that affects peripheral motor and sensory nerves as well as the cranial auditory and vestibular nerves.

A 64-year-old woman with night paroxysmal episodes is described. Her symptoms began 9 months ago with attacks of bizarre movement, which were always present in the second part of the night. She had no attacks during the daytime. Her husband reported confusion and disorientation followed by long periods of unresponsiveness. The patient underwent a night polysomnography recording. Around 4 o'clock in the morning bizarre movements with stereotypic behaviour appeared. She was rolling her head from side to side, moaning, and stretching her limbs. These periods first lasted for minutes, and were constantly repeated during the night. EEG findings suggested metabolic encephalopathy. At that time finger prick test revealed a profound hypoglycaemia (1.2 mmol/l), high insulin (200 pmol/l), and C-peptide (6.63 nmol/l). Ultrasonography and MRI confirmed the insulinoma in the head of the pancreas. To our knowledge our case is the first patient with insulinoma attacks only during sleep time.

Objective: To define auditory nerve and cochlear functions in two families with autosomal dominant axonal Charcot-Marie-Tooth (CMT)., Methods: Affected members in two families with different point mutations of NF-L gene were screened with auditory brainstem responses (ABRs). Those with abnormal ABRs were further investigated with clinical, neurophysiological and audiological procedures. The point mutations of NF-L gene involved were Glu397Lys in 8 affected members of the family with AN, and Pro22Ser in 9 affected members of the family without AN., Results: ABRs and stapedial muscle reflexes were absent or abnormal in affected members of only one family consistent with auditory neuropathy (AN). In them, audiograms, otoacoustic emissions, and speech comprehension were normal. Absent or abnormal ABRs were consistent with slowing of conduction along auditory nerve and/or brainstem auditory pathway. Wave I when present was of normal latency., Conclusions: Auditory nerve involvement in the presence of normal cochlear outer hair cell activity is asymptomatic in one of two families with CMT disorder with different point mutations of the NF-L gene. The nerve disorder is consistent with altered synchrony and slowed conduction., Significance: The absence of "deafness" may reflect the ability of central mechanisms to compensate for the slowly developing auditory nerve abnormalities.

In a Slovene Gypsy family of 19 subjects from four generations three patients with clinical characteristics compatible with hereditary motor and sensory neuropathy - Lom (HMSNL). were found They had severe distal and milder proximal muscle atrophy and weakness with areflexia of myotatic jerks. Two had facial weakness at the time when already wheelchair bound. All sensory modalities were affected distally in the limbs. Sluggish pupillary responses to light and convergence were found. They had skeletal abnormalities. One patient had polydactily on the hand. Nerve conduction studies were compatible with demyelinative polyneuropathy. Nerve biopsy showed mainly axonal loss without hypertrophic changes. Auditory neuropathy was diagnosed in all of them. None of the patients had duplication of 17p1.2-12 or point mutations in the Protein zero. Peripheral myelin protein and Connexin32 genes. Similar disorder that mapped to 8q24 was previously described in some Bulgarian and Italian Gypsy families. Members of our family may suffer from the same hereditary disease and may carry the same ancestor mutation, which was in the past spread in European Gypsy populations.

Follow-up brainstem auditory evoked potential (BAEP) and somatosensory evoked potential (SEP) studies were performed within 72 hours after admission in 127 children with severe head injury (Glasgow Coma Scale score of < or = 8) in order to predict quo ad vitam outcome of posttraumatic coma. Outcomes were categorised as brain death and survival. On first assessment 50 comatose children had normal BAEPs and SEPs. 78% of them survived and 22% deteriorated and died. 45 had abnormal findings. 69% of them improved and survived whilst 31% deteriorated and died. 32 children did not have recordable BAEPs and SEPs. All of them died. Thus, comatose children with normal EP studies have in 78% good prognosis and a bad outcome can be reliably predicted.

Progressive encephalopathy, developmental delay, microcephaly, electroencephalogram (EEG) and computed tomographic (CT) scan abnormalities have been reported in 80% of children with chronic renal failure (CRF) in infancy. Malnutrition, aluminium intoxication and psychosocial deprivation are proposed as causes. In 15 children with CRF from infancy we evaluated the effect of no aluminium salts and early vigorous nutritional and psychosocial support, in addition to the standard therapy, on neurological development. Six patients underwent dialysis (2 at birth) and 3 received transplants. None of our patients were given aluminium therapy. The nutritional status of the patients in the first 2 years of life was assessed with the waterlow classification. At the end of the follow-up period (mean 50 months range 14-148 months), patients underwent neurodevelopmental assessment, head CT scan, EEG, nerve conduction velocity (NCV) and auditory brain stem evoked response (ABER). None of our patients developed progressive encephalopathy or recurrent seizures. All have a normal neurological examination apart from hypotonia. Microcephaly was present in 5 patients. There was a good correlation between malnutrition in the first 2 years of life and microcephaly. Developmental delay was present in 3 patients; all 3 were microcephalic. There was evidence of brain atrophy on CT scan in only 3 patients. EEG was abnormal in 6 patients, but only severe in 1 patient. Only 1 patient had diminished NCV; all patients had a normal ABER. We conclude that a policy of no oral aluminium therapy and early nutritional support leads to better neurological outcome in children with CRF from infancy.

Twelve patients with Wilson's disease, aged 11-25 years, underwent brainstem auditory evoked potential (BAEP) study. The results were correlated to clinical, neuroradiological and laboratory data. Ten had prominent to severe neurological manifestations, suggestive of involvement of one or several CNS structures, and 2 were neurologically free. All had evidence of abnormal copper metabolism, and 8 had CT scan evidence of brain atrophy, or hypodense areas in basal ganglia, or both. The 2 patients without neurological manifestations as well as one with neurological signs had normal BAEP. One patient with neurological signs had increased N1 latency due to cochlear hearing loss, but normal interpeak intervals, while 8 of 10 patients with prominent neurological symptoms and signs had abnormal BAEPs (prolongation of NIII-NV interpeak interval). The value of NIII-NV interpeak interval correlated with the number of different neurological signs (neurological score) attributable to involvement of different CNS structures (r = 0.64 at P = 0.001). Abnormal BAEPs do not seem to be an early finding in Wilson's disease.

Twelve patients with neurobrucellosis and 17 patients with systemic brucellosis without neurological involvement underwent a brainstem auditory evoked potentials (BAEP) study. All neurobrucellosis patients (100%) showed abnormalities in their BAEP recordings, suggestive of brainstem lesions at various levels. On the other hand, only 5 (29%) of the 17 patients with systemic brucellosis had mild unilateral BAEP abnormalities, while the remaining 12 had normal responses. Comparison of pooled data between the systemic brucellosis and neurobrucellosis groups showed highly significant differences in all BAEP parameters. The recording of BAEP is thus considered a sensitive supplementary method to reveal CNS lesions in patients with neurobrucellosis.

The Kearns-Sayre syndrome is an uncommon disease, characterized by the triad of external ophthalmoplegia, retinitis pigmentosa, and heart block. Cardiac manifestations of this syndrome in a 31-year-old man are presented. Electrocardiogram revealed intermittent left bundle branch block and right bundle branch block with left anterior hemiblock. His bundle recording disclosed a prolonged HV interval. Clinical features of the syndrome are discussed and other published cases reviewed.

The aim of the present work was to establish whether contingent negative variation audiometry (CNV-A) is applicable to children. In a group of 23 children aged 5-7 years, only 10 generated clearly recognizable CNV when tested with the method successfully used in adults. When the procedure was modified by prolonging the S1-S2 interval and by introducing attractive slides to serve as the S2 stimulus and by adopting a slower repetition rate, 9 children randomly selected from the former group generated high-amplitude CNV (10.1 +/- 4 mu V). The CNV-A measurements involving a longer auditory stimulus (S1), lasting nearly to the beginning of S2, and an even slower repetition rate were equally successful in 18 children aged 3-5 years, who generated CNV with an average amplitude of about 9 mu V (range 5-15 mu V). We believe that the basic problem of successful CNV recording in children is to attract their attention to the signals of the CNV paradigm. The child's attentiveness decreases rapidly. The mean difference and the absolute mean difference between the subjective hearing threshold for white noise and the perception threshold for white noise as determined by CNV-A were as follows: 8.8 +/- 8 dB (both values) for the older group, and 3 +/- 10.4 and 8.6 +/- 6.5 dB, respectively, for the younger group. These differences are quite comparable to those obtained in adults. We therefore believe that CNV-A, used in combination with the behavioral method, provides a most reliable estimate of the child's hearing threshold in dubious situations.