Giuseppe Caruso

Although the involvement of large myelinated sensory fibers in Friedreich's ataxia (FA) is well documented, an impairment of unmyelinated fibers has not been described. We demonstrate an involvement of cutaneous unmyelinated sensory and autonomic nerve fibers in FA patients. We performed a morphological and functional study of cutaneous nerve fibers in 14 FA patients and in a population of control subjects. We used immunohistochemical techniques and confocal microscopy applied to punch skin biopsies from thigh, distal leg, and fingertip, and compared the density of epidermal nerve fibers (ENFs) with the results of mechanical pain sensation and thermal and tactile thresholds performed on hand dorsum, thigh, distal leg, and foot dorsum. We observed in our patients a statistically significant loss of ENFs, a reduced innervation of sweat glands, arrector pilorum muscles and arterioles, and an impairment of thermal and tactile thresholds and mechanical pain detection.

A clinical and electrophysiological follow-up was carried out for 3 to 7 years on 15 patients with Friedreich's ataxia (FA). Sural nerve biopsy was performed once in all patients, and a second time 6–7 years later in three of them. Clinical worsening and progression of disturbance were evaluated according to IAP and IACR scales. Sensory orthodromic conduction along median and tibial nerves was typical of FA and did not change between first and last examinations, nor were there morphological changes between the first and the second sural nerve biopsies. Peripheral nerve involvement is thought to be a result of defective development of the largest neurons and to remain stable from a very early stage of the disease; the clinical worsening may then be due to a progressive involvement of the pyramidal tracts and the cerebellar pathways.

A clinical and electrophysiological follow-up was carried out for 3 to 7 years on 15 patients with Friedreich's ataxia (FA). Sural nerve biopsy was performed once in all patients, and a second time 6–7 years later in three of them. Clinical worsening and progression of disturbance were evaluated according to IAP and IACR scales. Sensory orthodromic conduction along median and tibial nerves was typical of FA and did not change between first and last examinations, nor were there morphological changes between the first and the second sural nerve biopsies. Peripheral nerve involvement is thought to be a result of defective development of the largest neurons and to remain stable from a very early stage of the disease; the clinical worsening may then be due to a progressive involvement of the pyramidal tracts and the cerebellar pathways.

A multimodal electrophysiological study was performed on 41 patients from 24 families with autosomal dominant cerebellar ataxia type I (ADCA I). Upper- and lower-limb motor evoked potentials (MEPs) to transcranial magnetic stimulation, median and tibial nerve somatosensory evoked potentials (Mn and Tn-SSEPs), orthodromic sensory (SCV) and motor conduction (MCV) velocity along median and tibial nerve, brainstem auditory evoked potentials (BAEPs), and visual evoked potentials (VEPs) were examined. Molecular analysis showed 2 SCA1 families and 2 families linked to the SCA2 locus. A sural nerve biopsy was performed in 5 patients. Brainstem damage of the auditory pathway was observed in 79% of patients examined. VEP abnormalities possibly of central origin were found in 52% of patients. MEP and SSEP abnormalities were differently distributed along the pathways examined: the longer the pathway, the higher the occurrence and severity of impairment. Peripheral dying-back neuropathy (confirmed by nerve bioptic data) was a frequent finding (56%). A progressive degenerative process involving first the longest tracts of the central motor and central and peripheral branches of somatosensory pathways is hypothesized in ADCA I. MEP abnormalities were more frequent in SCA1, and the sensory-motor neuropathy was more severe in SCA2.

ABSTRACT- Electromyography was performed, and motor and sensory nerve conduction velocities were measured in 19 patients definitely affected by Friedreich's ataxia. Biopsy of the sural nerve was also performed in 9 patients.Most patients presented a moderate to severe loss of motor units, a significant increase in mean duration of motor unit potentials, and in the incidence of polyphasic potentials. Short-lasting spontaneous activity was rarely seen. Conduction velocity along the motor and sensory fibres of the median and tibial nerves was moderately slowed, while distal conduction time to muscle was significantly increased and the sensory orthodromicallyevoked response markedly reduced. Intraoperative electrophysiological recordings obtained during biopsy of the sural nerve in 4 patients were consistent with the changes conventionally observed in the median, tibial and sural (6 patients) nerves.Quantitative histology revealed a reduced number of total myelinated fibres with a severe loss of large fibres, and a moderate loss of fibres of less than 7 μm in diameter. In teased nerve fibre preparations, the most evident abnormality consisted of fibres with uniformly short internodal length, while signs of remyelination were less prominent. Signs of active axonal degeneration were rarely observed in electron microscopy.Electrophysiological and histological findings were uniformly distributed, and the changes were neither related to the duration nor to the severity of the clinical condition.

Two hundred and forty-eight patients from 116 Italian families with dominant ataxia were studied for CAG expansion within SCA1, 2, 3, 6, 7 (spinocerebellar ataxia) and DRPLA (dentatorubropallidoluysian atrophy) genes. Fifty-six percent of the families originated from Southern, 19% from Central and 25% from Northern Italy. SCA2 was the commonest mutation, accounting for 47% of the families, followed by SCA1 (24%), SCA6 (2%), SCA7 (2%) and DRPLA (1%). No SCA3 family was found. Twenty-four percent of the families carried a still unidentified mutation. When occurrence of mutations was evaluated according to the geographic origin, SCA1 was the commonest in Northern (72%), whereas SCA2 was prevalent (63%) in Southern Italy. The number of CAG repeats in SCA1 normal alleles was higher in Northern than in Central-Southern Italy.

Motor evoked potentials (MEPs) from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles elicited by transcranial magnetic stimulation of the motor cortex were studied in 15 patients with Alzheimer disease (AD). An abnormally higher MEP threshold in APB, frequently associated with absence of the MEP in relaxed TA muscles, was found in 40% of patients, almost all of them

Peripheral nerve conduction velocity and cortical evoked potentials were investigated in 48 patients with Friedreich's disease and in 35 relatives. There were 14 patients and 2 relatives who underwent sural nerve biopsy.In the patients sensory conduction velocity was moderately slowed, whereas sensory responses were markedly reduced. Nerve biopsy showed a severe loss of large myelinated fibers and no demyelination. On teased nerve fiber preparations, most fibers presented uniformly short internodes. No correlation was seen between sensory conduction findings or histologic abnormalities and clinical disability.In patients SSEP changes, which were constant, and VEPs, which were frequently involved, were unrelated to the severity or duration of clinical disability.The were 14 relatives who showed clinical signs of Friedreich's disease. Slightly decreased distal conduction velocity along sensory fibers was observed in more than half of the relatives. Nerve biopsy was noncontributory. In conclusion, we could not determine whether the abnormalities observed in the siblings were an expression of a heterozygotic condition, or whether they were early signs of the disease.

A multimodal electrophysiological study was performed on 41 patients from 24 families with autosomal dominant cerebellar ataxia type I (ADCA I). Upper- and lower-limb motor evoked potentials (MEPs) to transcranial magnetic stimulation, median and tibial nerve somatosensory evoked potentials (Mn and Tn-SSEPs), orthodromic sensory (SCV) and motor conduction (MCV) velocity along median and tibial nerve, brainstem auditory evoked potentials (BAEPs), and visual evoked potentials (VEPs) were examined. Molecular analysis showed 2 SCA1 families and 2 families linked to the SCA2 locus. A sural nerve biopsy was performed in 5 patients. Brainstem damage of the auditory pathway was observed in 79% of patients examined. VEP abnormalities possibly of central origin were found in 52% of patients. MEP and SSEP abnormalities were differently distributed along the pathways examined: the longer the pathway, the higher the occurrence and severity of impairment. Peripheral dying-back neuropathy (confirmed by nerve bioptic data) was a frequent finding (56%). A progressive degenerative process involving first the longest tracts of the central motor and central and peripheral branches of somatosensory pathways is hypothesized in ADCA I. MEP abnormalities were more frequent in SCA1, and the sensory-motor neuropathy was more severe in SCA2.

The clinical and genetic features of 80 patients with Friedreich's disease from 64 families are described. Diagnostic criteria were: no evidence of dominant inheritance, onset by the age of 20 years, progressive unremitting ataxia of limbs and gait, and absence of knee and ankle jerks. Furthermore, at least one of the following accessory signs was present: dysarthria, extensor plantar response and echocardiographic evidence of hypertrophic cardiomyopathy. Two peaks of onset age were evident at 6–9 and 12–15 years. Analysis of intrafamily variation of onset age and absence of clustering of cardiomyopathy and diabetes did not suggest genetic heterogeneity. Peripheral nerve impairment was an early finding and showed slight further progression, whereas involvement of the cerebellar and corticospinal pathways appeared later and mainly accounted for the progressive worsening of the disease.

The clinical and genetic features of 80 patients with Friedreich's disease from 64 families are described. Diagnostic criteria were: no evidence of dominant inheritance, onset by the age of 20 years, progressive unremitting ataxia of limbs and gait, and absence of knee and ankle jerks. Furthermore, at least one of the following accessory signs was present: dysarthria, extensor plantar response and echocardiographic evidence of hypertrophic cardiomyopathy. Two peaks of onset age were evident at 6–9 and 12–15 years. Analysis of intrafamily variation of onset age and absence of clustering of cardiomyopathy and diabetes did not suggest genetic heterogeneity. Peripheral nerve impairment was an early finding and showed slight further progression, whereas involvement of the cerebellar and corticospinal pathways appeared later and mainly accounted for the progressive worsening of the disease.

Although the involvement of large myelinated sensory fibers in Friedreich's ataxia (FA) is well documented, an impairment of unmyelinated fibers has not been described. We demonstrate an involvement of cutaneous unmyelinated sensory and autonomic nerve fibers in FA patients. We performed a morphological and functional study of cutaneous nerve fibers in 14 FA patients and in a population of control subjects. We used immunohistochemical techniques and confocal microscopy applied to punch skin biopsies from thigh, distal leg, and fingertip, and compared the density of epidermal nerve fibers (ENFs) with the results of mechanical pain sensation and thermal and tactile thresholds performed on hand dorsum, thigh, distal leg, and foot dorsum. We observed in our patients a statistically significant loss of ENFs, a reduced innervation of sweat glands, arrector pilorum muscles and arterioles, and an impairment of thermal and tactile thresholds and mechanical pain detection.

A multimodal electrophysiological study was performed on 41 patients from 24 families with autosomal dominant cerebellar ataxia type I (ADCA I). Upper- and lower-limb motor evoked potentials (MEPs) to transcranial magnetic stimulation, median and tibial nerve somatosensory evoked potentials (Mn and Tn-SSEPs), orthodromic sensory (SCV) and motor conduction (MCV) velocity along median and tibial nerve, brainstem auditory evoked potentials (BAEPs), and visual evoked potentials (VEPs) were examined. Molecular analysis showed 2 SCA1 families and 2 families linked to the SCA2 locus. A sural nerve biopsy was performed in 5 patients. Brainstem damage of the auditory pathway was observed in 79% of patients examined. VEP abnormalities possibly of central origin were found in 52% of patients. MEP and SSEP abnormalities were differently distributed along the pathways examined: the longer the pathway, the higher the occurrence and severity of impairment. Peripheral dying-back neuropathy (confirmed by nerve bioptic data) was a frequent finding (56%). A progressive degenerative process involving first the longest tracts of the central motor and central and peripheral branches of somatosensory pathways is hypothesized in ADCA I. MEP abnormalities were more frequent in SCA1, and the sensory-motor neuropathy was more severe in SCA2.

A clinical and electrophysiological follow-up was carried out for 3 to 7 years on 15 patients with Friedreich's ataxia (FA). Sural nerve biopsy was performed once in all patients, and a second time 6–7 years later in three of them. Clinical worsening and progression of disturbance were evaluated according to IAP and IACR scales. Sensory orthodromic conduction along median and tibial nerves was typical of FA and did not change between first and last examinations, nor were there morphological changes between the first and the second sural nerve biopsies. Peripheral nerve involvement is thought to be a result of defective development of the largest neurons and to remain stable from a very early stage of the disease; the clinical worsening may then be due to a progressive involvement of the pyramidal tracts and the cerebellar pathways.

Although the involvement of large myelinated sensory fibers in Friedreich's ataxia (FA) is well documented, an impairment of unmyelinated fibers has not been described. We demonstrate an involvement of cutaneous unmyelinated sensory and autonomic nerve fibers in FA patients. We performed a morphological and functional study of cutaneous nerve fibers in 14 FA patients and in a population of control subjects. We used immunohistochemical techniques and confocal microscopy applied to punch skin biopsies from thigh, distal leg, and fingertip, and compared the density of epidermal nerve fibers (ENFs) with the results of mechanical pain sensation and thermal and tactile thresholds performed on hand dorsum, thigh, distal leg, and foot dorsum. We observed in our patients a statistically significant loss of ENFs, a reduced innervation of sweat glands, arrector pilorum muscles and arterioles, and an impairment of thermal and tactile thresholds and mechanical pain detection.

The clinical and genetic features of 80 patients with Friedreich's disease from 64 families are described. Diagnostic criteria were: no evidence of dominant inheritance, onset by the age of 20 years, progressive unremitting ataxia of limbs and gait, and absence of knee and ankle jerks. Furthermore, at least one of the following accessory signs was present: dysarthria, extensor plantar response and echocardiographic evidence of hypertrophic cardiomyopathy. Two peaks of onset age were evident at 6–9 and 12–15 years. Analysis of intrafamily variation of onset age and absence of clustering of cardiomyopathy and diabetes did not suggest genetic heterogeneity. Peripheral nerve impairment was an early finding and showed slight further progression, whereas involvement of the cerebellar and corticospinal pathways appeared later and mainly accounted for the progressive worsening of the disease.

ABSTRACT- Electromyography was performed, and motor and sensory nerve conduction velocities were measured in 19 patients definitely affected by Friedreich's ataxia. Biopsy of the sural nerve was also performed in 9 patients.Most patients presented a moderate to severe loss of motor units, a significant increase in mean duration of motor unit potentials, and in the incidence of polyphasic potentials. Short-lasting spontaneous activity was rarely seen. Conduction velocity along the motor and sensory fibres of the median and tibial nerves was moderately slowed, while distal conduction time to muscle was significantly increased and the sensory orthodromicallyevoked response markedly reduced. Intraoperative electrophysiological recordings obtained during biopsy of the sural nerve in 4 patients were consistent with the changes conventionally observed in the median, tibial and sural (6 patients) nerves.Quantitative histology revealed a reduced number of total myelinated fibres with a severe loss of large fibres, and a moderate loss of fibres of less than 7 μm in diameter. In teased nerve fibre preparations, the most evident abnormality consisted of fibres with uniformly short internodal length, while signs of remyelination were less prominent. Signs of active axonal degeneration were rarely observed in electron microscopy.Electrophysiological and histological findings were uniformly distributed, and the changes were neither related to the duration nor to the severity of the clinical condition.

A clinical and electrophysiological follow-up was carried out for 3 to 7 years on 15 patients with Friedreich's ataxia (FA). Sural nerve biopsy was performed once in all patients, and a second time 6–7 years later in three of them. Clinical worsening and progression of disturbance were evaluated according to IAP and IACR scales. Sensory orthodromic conduction along median and tibial nerves was typical of FA and did not change between first and last examinations, nor were there morphological changes between the first and the second sural nerve biopsies. Peripheral nerve involvement is thought to be a result of defective development of the largest neurons and to remain stable from a very early stage of the disease; the clinical worsening may then be due to a progressive involvement of the pyramidal tracts and the cerebellar pathways.

Motor evoked potentials (MEPs) from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles elicited by transcranial magnetic stimulation of the motor cortex were studied in 15 patients with Alzheimer disease (AD). An abnormally higher MEP threshold in APB, frequently associated with absence of the MEP in relaxed TA muscles, was found in 40% of patients, almost all of them

Peripheral nerve conduction velocity and cortical evoked potentials were investigated in 48 patients with Friedreich's disease and in 35 relatives. There were 14 patients and 2 relatives who underwent sural nerve biopsy.In the patients sensory conduction velocity was moderately slowed, whereas sensory responses were markedly reduced. Nerve biopsy showed a severe loss of large myelinated fibers and no demyelination. On teased nerve fiber preparations, most fibers presented uniformly short internodes. No correlation was seen between sensory conduction findings or histologic abnormalities and clinical disability.In patients SSEP changes, which were constant, and VEPs, which were frequently involved, were unrelated to the severity or duration of clinical disability.The were 14 relatives who showed clinical signs of Friedreich's disease. Slightly decreased distal conduction velocity along sensory fibers was observed in more than half of the relatives. Nerve biopsy was noncontributory. In conclusion, we could not determine whether the abnormalities observed in the siblings were an expression of a heterozygotic condition, or whether they were early signs of the disease.

Motor evoked potentials (MEPs) from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles elicited by transcranial magnetic stimulation of the motor cortex were studied in 15 patients with Alzheimer disease (AD). An abnormally higher MEP threshold in APB, frequently associated with absence of the MEP in relaxed TA muscles, was found in 40% of patients, almost all of them

Two hundred and forty-eight patients from 116 Italian families with dominant ataxia were studied for CAG expansion within SCA1, 2, 3, 6, 7 (spinocerebellar ataxia) and DRPLA (dentatorubropallidoluysian atrophy) genes. Fifty-six percent of the families originated from Southern, 19% from Central and 25% from Northern Italy. SCA2 was the commonest mutation, accounting for 47% of the families, followed by SCA1 (24%), SCA6 (2%), SCA7 (2%) and DRPLA (1%). No SCA3 family was found. Twenty-four percent of the families carried a still unidentified mutation. When occurrence of mutations was evaluated according to the geographic origin, SCA1 was the commonest in Northern (72%), whereas SCA2 was prevalent (63%) in Southern Italy. The number of CAG repeats in SCA1 normal alleles was higher in Northern than in Central-Southern Italy.

ABSTRACT- Electromyography was performed, and motor and sensory nerve conduction velocities were measured in 19 patients definitely affected by Friedreich's ataxia. Biopsy of the sural nerve was also performed in 9 patients.Most patients presented a moderate to severe loss of motor units, a significant increase in mean duration of motor unit potentials, and in the incidence of polyphasic potentials. Short-lasting spontaneous activity was rarely seen. Conduction velocity along the motor and sensory fibres of the median and tibial nerves was moderately slowed, while distal conduction time to muscle was significantly increased and the sensory orthodromicallyevoked response markedly reduced. Intraoperative electrophysiological recordings obtained during biopsy of the sural nerve in 4 patients were consistent with the changes conventionally observed in the median, tibial and sural (6 patients) nerves.Quantitative histology revealed a reduced number of total myelinated fibres with a severe loss of large fibres, and a moderate loss of fibres of less than 7 μm in diameter. In teased nerve fibre preparations, the most evident abnormality consisted of fibres with uniformly short internodal length, while signs of remyelination were less prominent. Signs of active axonal degeneration were rarely observed in electron microscopy.Electrophysiological and histological findings were uniformly distributed, and the changes were neither related to the duration nor to the severity of the clinical condition.

Peripheral nerve conduction velocity and cortical evoked potentials were investigated in 48 patients with Friedreich's disease and in 35 relatives. There were 14 patients and 2 relatives who underwent sural nerve biopsy.In the patients sensory conduction velocity was moderately slowed, whereas sensory responses were markedly reduced. Nerve biopsy showed a severe loss of large myelinated fibers and no demyelination. On teased nerve fiber preparations, most fibers presented uniformly short internodes. No correlation was seen between sensory conduction findings or histologic abnormalities and clinical disability.In patients SSEP changes, which were constant, and VEPs, which were frequently involved, were unrelated to the severity or duration of clinical disability.The were 14 relatives who showed clinical signs of Friedreich's disease. Slightly decreased distal conduction velocity along sensory fibers was observed in more than half of the relatives. Nerve biopsy was noncontributory. In conclusion, we could not determine whether the abnormalities observed in the siblings were an expression of a heterozygotic condition, or whether they were early signs of the disease.

Motor evoked potentials (MEPs) from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles elicited by transcranial magnetic stimulation of the motor cortex were studied in 15 patients with Alzheimer disease (AD). An abnormally higher MEP threshold in APB, frequently associated with absence of the MEP in relaxed TA muscles, was found in 40% of patients, almost all of them

ABSTRACT- Electromyography was performed, and motor and sensory nerve conduction velocities were measured in 19 patients definitely affected by Friedreich's ataxia. Biopsy of the sural nerve was also performed in 9 patients.Most patients presented a moderate to severe loss of motor units, a significant increase in mean duration of motor unit potentials, and in the incidence of polyphasic potentials. Short-lasting spontaneous activity was rarely seen. Conduction velocity along the motor and sensory fibres of the median and tibial nerves was moderately slowed, while distal conduction time to muscle was significantly increased and the sensory orthodromicallyevoked response markedly reduced. Intraoperative electrophysiological recordings obtained during biopsy of the sural nerve in 4 patients were consistent with the changes conventionally observed in the median, tibial and sural (6 patients) nerves.Quantitative histology revealed a reduced number of total myelinated fibres with a severe loss of large fibres, and a moderate loss of fibres of less than 7 μm in diameter. In teased nerve fibre preparations, the most evident abnormality consisted of fibres with uniformly short internodal length, while signs of remyelination were less prominent. Signs of active axonal degeneration were rarely observed in electron microscopy.Electrophysiological and histological findings were uniformly distributed, and the changes were neither related to the duration nor to the severity of the clinical condition.

Peripheral nerve conduction velocity and cortical evoked potentials were investigated in 48 patients with Friedreich's disease and in 35 relatives. There were 14 patients and 2 relatives who underwent sural nerve biopsy.In the patients sensory conduction velocity was moderately slowed, whereas sensory responses were markedly reduced. Nerve biopsy showed a severe loss of large myelinated fibers and no demyelination. On teased nerve fiber preparations, most fibers presented uniformly short internodes. No correlation was seen between sensory conduction findings or histologic abnormalities and clinical disability.In patients SSEP changes, which were constant, and VEPs, which were frequently involved, were unrelated to the severity or duration of clinical disability.The were 14 relatives who showed clinical signs of Friedreich's disease. Slightly decreased distal conduction velocity along sensory fibers was observed in more than half of the relatives. Nerve biopsy was noncontributory. In conclusion, we could not determine whether the abnormalities observed in the siblings were an expression of a heterozygotic condition, or whether they were early signs of the disease.

A multimodal electrophysiological study was performed on 41 patients from 24 families with autosomal dominant cerebellar ataxia type I (ADCA I). Upper- and lower-limb motor evoked potentials (MEPs) to transcranial magnetic stimulation, median and tibial nerve somatosensory evoked potentials (Mn and Tn-SSEPs), orthodromic sensory (SCV) and motor conduction (MCV) velocity along median and tibial nerve, brainstem auditory evoked potentials (BAEPs), and visual evoked potentials (VEPs) were examined. Molecular analysis showed 2 SCA1 families and 2 families linked to the SCA2 locus. A sural nerve biopsy was performed in 5 patients. Brainstem damage of the auditory pathway was observed in 79% of patients examined. VEP abnormalities possibly of central origin were found in 52% of patients. MEP and SSEP abnormalities were differently distributed along the pathways examined: the longer the pathway, the higher the occurrence and severity of impairment. Peripheral dying-back neuropathy (confirmed by nerve bioptic data) was a frequent finding (56%). A progressive degenerative process involving first the longest tracts of the central motor and central and peripheral branches of somatosensory pathways is hypothesized in ADCA I. MEP abnormalities were more frequent in SCA1, and the sensory-motor neuropathy was more severe in SCA2.

A clinical and electrophysiological follow-up was carried out for 3 to 7 years on 15 patients with Friedreich's ataxia (FA). Sural nerve biopsy was performed once in all patients, and a second time 6–7 years later in three of them. Clinical worsening and progression of disturbance were evaluated according to IAP and IACR scales. Sensory orthodromic conduction along median and tibial nerves was typical of FA and did not change between first and last examinations, nor were there morphological changes between the first and the second sural nerve biopsies. Peripheral nerve involvement is thought to be a result of defective development of the largest neurons and to remain stable from a very early stage of the disease; the clinical worsening may then be due to a progressive involvement of the pyramidal tracts and the cerebellar pathways.

Peripheral nerve conduction velocity and cortical evoked potentials were investigated in 48 patients with Friedreich's disease and in 35 relatives. There were 14 patients and 2 relatives who underwent sural nerve biopsy.In the patients sensory conduction velocity was moderately slowed, whereas sensory responses were markedly reduced. Nerve biopsy showed a severe loss of large myelinated fibers and no demyelination. On teased nerve fiber preparations, most fibers presented uniformly short internodes. No correlation was seen between sensory conduction findings or histologic abnormalities and clinical disability.In patients SSEP changes, which were constant, and VEPs, which were frequently involved, were unrelated to the severity or duration of clinical disability.The were 14 relatives who showed clinical signs of Friedreich's disease. Slightly decreased distal conduction velocity along sensory fibers was observed in more than half of the relatives. Nerve biopsy was noncontributory. In conclusion, we could not determine whether the abnormalities observed in the siblings were an expression of a heterozygotic condition, or whether they were early signs of the disease.

Two hundred and forty-eight patients from 116 Italian families with dominant ataxia were studied for CAG expansion within SCA1, 2, 3, 6, 7 (spinocerebellar ataxia) and DRPLA (dentatorubropallidoluysian atrophy) genes. Fifty-six percent of the families originated from Southern, 19% from Central and 25% from Northern Italy. SCA2 was the commonest mutation, accounting for 47% of the families, followed by SCA1 (24%), SCA6 (2%), SCA7 (2%) and DRPLA (1%). No SCA3 family was found. Twenty-four percent of the families carried a still unidentified mutation. When occurrence of mutations was evaluated according to the geographic origin, SCA1 was the commonest in Northern (72%), whereas SCA2 was prevalent (63%) in Southern Italy. The number of CAG repeats in SCA1 normal alleles was higher in Northern than in Central-Southern Italy.

ABSTRACT- Electromyography was performed, and motor and sensory nerve conduction velocities were measured in 19 patients definitely affected by Friedreich's ataxia. Biopsy of the sural nerve was also performed in 9 patients.Most patients presented a moderate to severe loss of motor units, a significant increase in mean duration of motor unit potentials, and in the incidence of polyphasic potentials. Short-lasting spontaneous activity was rarely seen. Conduction velocity along the motor and sensory fibres of the median and tibial nerves was moderately slowed, while distal conduction time to muscle was significantly increased and the sensory orthodromicallyevoked response markedly reduced. Intraoperative electrophysiological recordings obtained during biopsy of the sural nerve in 4 patients were consistent with the changes conventionally observed in the median, tibial and sural (6 patients) nerves.Quantitative histology revealed a reduced number of total myelinated fibres with a severe loss of large fibres, and a moderate loss of fibres of less than 7 μm in diameter. In teased nerve fibre preparations, the most evident abnormality consisted of fibres with uniformly short internodal length, while signs of remyelination were less prominent. Signs of active axonal degeneration were rarely observed in electron microscopy.Electrophysiological and histological findings were uniformly distributed, and the changes were neither related to the duration nor to the severity of the clinical condition.

The clinical and genetic features of 80 patients with Friedreich's disease from 64 families are described. Diagnostic criteria were: no evidence of dominant inheritance, onset by the age of 20 years, progressive unremitting ataxia of limbs and gait, and absence of knee and ankle jerks. Furthermore, at least one of the following accessory signs was present: dysarthria, extensor plantar response and echocardiographic evidence of hypertrophic cardiomyopathy. Two peaks of onset age were evident at 6–9 and 12–15 years. Analysis of intrafamily variation of onset age and absence of clustering of cardiomyopathy and diabetes did not suggest genetic heterogeneity. Peripheral nerve impairment was an early finding and showed slight further progression, whereas involvement of the cerebellar and corticospinal pathways appeared later and mainly accounted for the progressive worsening of the disease.

Although the involvement of large myelinated sensory fibers in Friedreich's ataxia (FA) is well documented, an impairment of unmyelinated fibers has not been described. We demonstrate an involvement of cutaneous unmyelinated sensory and autonomic nerve fibers in FA patients. We performed a morphological and functional study of cutaneous nerve fibers in 14 FA patients and in a population of control subjects. We used immunohistochemical techniques and confocal microscopy applied to punch skin biopsies from thigh, distal leg, and fingertip, and compared the density of epidermal nerve fibers (ENFs) with the results of mechanical pain sensation and thermal and tactile thresholds performed on hand dorsum, thigh, distal leg, and foot dorsum. We observed in our patients a statistically significant loss of ENFs, a reduced innervation of sweat glands, arrector pilorum muscles and arterioles, and an impairment of thermal and tactile thresholds and mechanical pain detection.

Two hundred and forty-eight patients from 116 Italian families with dominant ataxia were studied for CAG expansion within SCA1, 2, 3, 6, 7 (spinocerebellar ataxia) and DRPLA (dentatorubropallidoluysian atrophy) genes. Fifty-six percent of the families originated from Southern, 19% from Central and 25% from Northern Italy. SCA2 was the commonest mutation, accounting for 47% of the families, followed by SCA1 (24%), SCA6 (2%), SCA7 (2%) and DRPLA (1%). No SCA3 family was found. Twenty-four percent of the families carried a still unidentified mutation. When occurrence of mutations was evaluated according to the geographic origin, SCA1 was the commonest in Northern (72%), whereas SCA2 was prevalent (63%) in Southern Italy. The number of CAG repeats in SCA1 normal alleles was higher in Northern than in Central-Southern Italy.

The clinical and genetic features of 80 patients with Friedreich's disease from 64 families are described. Diagnostic criteria were: no evidence of dominant inheritance, onset by the age of 20 years, progressive unremitting ataxia of limbs and gait, and absence of knee and ankle jerks. Furthermore, at least one of the following accessory signs was present: dysarthria, extensor plantar response and echocardiographic evidence of hypertrophic cardiomyopathy. Two peaks of onset age were evident at 6–9 and 12–15 years. Analysis of intrafamily variation of onset age and absence of clustering of cardiomyopathy and diabetes did not suggest genetic heterogeneity. Peripheral nerve impairment was an early finding and showed slight further progression, whereas involvement of the cerebellar and corticospinal pathways appeared later and mainly accounted for the progressive worsening of the disease.

A multimodal electrophysiological study was performed on 41 patients from 24 families with autosomal dominant cerebellar ataxia type I (ADCA I). Upper- and lower-limb motor evoked potentials (MEPs) to transcranial magnetic stimulation, median and tibial nerve somatosensory evoked potentials (Mn and Tn-SSEPs), orthodromic sensory (SCV) and motor conduction (MCV) velocity along median and tibial nerve, brainstem auditory evoked potentials (BAEPs), and visual evoked potentials (VEPs) were examined. Molecular analysis showed 2 SCA1 families and 2 families linked to the SCA2 locus. A sural nerve biopsy was performed in 5 patients. Brainstem damage of the auditory pathway was observed in 79% of patients examined. VEP abnormalities possibly of central origin were found in 52% of patients. MEP and SSEP abnormalities were differently distributed along the pathways examined: the longer the pathway, the higher the occurrence and severity of impairment. Peripheral dying-back neuropathy (confirmed by nerve bioptic data) was a frequent finding (56%). A progressive degenerative process involving first the longest tracts of the central motor and central and peripheral branches of somatosensory pathways is hypothesized in ADCA I. MEP abnormalities were more frequent in SCA1, and the sensory-motor neuropathy was more severe in SCA2.

Motor evoked potentials (MEPs) from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles elicited by transcranial magnetic stimulation of the motor cortex were studied in 15 patients with Alzheimer disease (AD). An abnormally higher MEP threshold in APB, frequently associated with absence of the MEP in relaxed TA muscles, was found in 40% of patients, almost all of them

Two hundred and forty-eight patients from 116 Italian families with dominant ataxia were studied for CAG expansion within SCA1, 2, 3, 6, 7 (spinocerebellar ataxia) and DRPLA (dentatorubropallidoluysian atrophy) genes. Fifty-six percent of the families originated from Southern, 19% from Central and 25% from Northern Italy. SCA2 was the commonest mutation, accounting for 47% of the families, followed by SCA1 (24%), SCA6 (2%), SCA7 (2%) and DRPLA (1%). No SCA3 family was found. Twenty-four percent of the families carried a still unidentified mutation. When occurrence of mutations was evaluated according to the geographic origin, SCA1 was the commonest in Northern (72%), whereas SCA2 was prevalent (63%) in Southern Italy. The number of CAG repeats in SCA1 normal alleles was higher in Northern than in Central-Southern Italy.