Influence of GAA expansion size and disease duration on central nervous system impairment in Friedreich's ataxia: contribution to the understanding of the pathophysiology of the disease.

OBJECTIVE: To verify if GAA expansion size could account for the severity of the central nervous system involvement in Friedreich's ataxia (FA). METHODS: Retrospective study of 52 FA patients (mean age 26.9+/-12.1 years; mean disease duration 10.6+/-7.6 years) homozygous for GAA expansion. Median nerve somatosensory evoked potentials (SSEPs) were available in 36 FA patients, upper limb motor evoked potentials (MEPs) to transcranial magnetic stimulation in 32, brainstem auditory evoked potentials (BAEPs) in 24, and visual evoked potentials (VEPs) in 34. N20, P100, MEP amplitude, SSEP and MEP central conduction time (CCT and CMCT), P100 latency and I-III and I-V interpeak latency, and a BAEP abnormality score were correlated with disease duration and GAA expansion size on the shorter (GAA1) and larger (GAA2) allele in each pair. RESULTS: The GAA1 size inversely correlated with the N20 amplitude (r = -0.49; P<0. 01). Disease duration directly correlated with CMCT (r = 0.57; P<0.01) and BAEP score (r = 0.61; P<0.01) and inversely with MEP (r = -0.40; P<0.05) and P100 amplitude (r = -0.39; P<0.05). CONCLUSIONS: Our data suggest that central somatosensory pathway involvement in FA is mainly determined by GAA1 expansion size. Vice versa, degeneration of pyramidal tracts, auditory and visual pathways seems to be a continuing process during the life of FA patients.     

Central motor conduction time by magnetic stimulation of the cortex and peripheral nerve conduction follow-up studies in Friedreich's ataxia

A follow-up clinical study, peripheral motor and sensory nerve conduction velocities and central motor conduction by magnetic stimulation of the cortex were performed in 13 patients with classical Friedreich's ataxia (FA) phenotype, for a period of 9–12 years. Clinical worsening was unrelated to peripheral nerve abnormalities. The amplitude of the nerve action potentials and delayed conduction velocity remained unchanged for several years. Central motor conduction times were abnormal in all patients. Clinical conditions worsened significantly between successive examinations with significant increments in threshold and significant decrement of the amplitude of motor evoked potentials. The results are consistent with progressive pyramidal and cerebellar pathways involvement as the cause of clinical worsening in FA.     

Evoked potentials in chronic n-hexane intoxication

Somatosensory, brainstem auditory and pattern-reversal visual evoked potentials (SEP, BAEP and PVEP) were studied in 5 patients with n-hexane polyneuropathy to determine if the CNS was affected. In SEPs, the median central conduction (N13-to-N20) was normal but the tibial central conduction (N22-to-P40) was delayed. The central conduction time (I-to-V interval) of the BAEP was also prolonged. However, the P100 latency of the PVEP was normal. The present data indicate that the spinal cord and the brainstem are primarily affected in chronic n-hexane intoxication.     

The clinical significance of the P15 wave of the somatosensory evoked potential in tentorial herniation

Somatosensory evoked potentials (SEPs) to median nerve stimulation and auditory brainstem evoked potentials (BAEPs) were recorded in 16 comatose patients who had suffered transtentorial herniation (TH) due to intracranial haematoma, hydrocephalus or tumour. An attempt was made to correlate the changes in the N14-P15 component of the central conduction time (CCT) and the I-V interpeak latencies (IPLs) of the BAEP with the clinical severity of TH. The N14-P15 component was not affected in seven patients at the diencephalic or early third-nerve stage, and six of these seven showed normal I-V IPLs. All six patients at the late third-nervel midbrain stage or worse, however, showed abnormalities in the N14-P15 components. Interestingly, five patients showed dissociation of SEP and BAEP abnormalities suggesting a differential sensitivity of the medial and lateral lemnisci in the brainstem to ischaemia and/or compression. All five patients in whom the P15 potential was absent on either side had a poor outcome and there was a correlation between the electrical failure in the N14-P15 component and the degree of brainstem damage caused by TH as assessed clinically. Reversible loss of the P15 potential by brainstem retraction has been shown in intraoperative SEP monitoring during aneurysm surgery. Prolonged compression of the upper brainstem seems to cause irreversible loss of the P15 which should be regarded as being due to irrecoverable brainstem dysfunction.     

The clinical significance of the P15 wave of the somatosensory evoked potential in tentorial herniation

Somatosensory evoked potentials (SEPs) to median nerve stimulation and auditory brainstem evoked potentials (BAEPs) were recorded in 16 comatose patients who had suffered transtentorial herniation (TH) due to intracranial haematoma, hydrocephalus or tumour. An attempt was made to correlate the changes in the N14-P15 component of the central conduction time (CCT) and the I-V interpeak latencies (IPLs) of the BAEP with the clinical severity of TH. The N14-P15 component was not affected in seven patients at the diencephalic or early third-nerve stage, and six of these seven showed normal I-V IPLs. All six patients at the late third-nerve/midbrain stage or worse, however, showed abnormalities in the N14-P15 components. Interestingly, five patients showed dissociation of SEP and BAEP abnormalities suggesting a differential sensitivity of the medial and lateral lemnisci in the brainstem to ischaemia and/or compression. All five patients in whom the P15 potential was absent on either side had a poor outcome and there was a correlation between the electrical failure in the N14-P15 component and the degree of brainstem damage caused by TH as assessed clinically. Reversible loss of the P15 potential by brainstem retraction has been shown in intraoperative SEP monitoring during aneurysm surgery. Prolonged compression of the upper brainstem seems to cause irreversible loss of the P15 which should be regarded as being due to irrecoverable brainstem dysfunction.     

Evoked potential abnormalities in the various inherited ataxias

Visual (VEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potential tests were performed in 45 patients representing ten types of inherited disorders in which ataxia was the most prominent symptom. Comparable VEP abnormalities were present among all types of patients. Normal BAEP tests were recorded in most patients except those with olivopontocerebellar atrophy. SEP results were often more severely abnormal in patients with Friedreich's ataxia. The observations emphasize the similarity in expression of different metabolic-degenerative disorders. When these tests are used clinically, certain features of evoked potentials (especially left-right symmetry) are typical of the inherited ataxias as a group. Few distinguishing features differentiate the individual disorders.     

Multimodality evoked potentials in amyotrophic lateral sclerosis

Visual, brainstem auditory and somatosensory evoked potentials to medial nerve stimulation were recorded in 27 patients affected by amyotrophic lateral sclerosis. VEP N75, P100, N140, N75-P100 latencies and P100 amplitude, BAEP I-III, III-V and I-V interpeak-latencies were within normal limits in all ALS patients. Somatosensory evoked potentials were abnormally delayed in 8 patients: in 3 arms because of a delayed N9-N13 latency, in 9 arms because of a delayed N13-N19 latency.     

Is early onset cerebellar ataxia with retained tendon reflexes identifiable by electrophysiologic and histologic profile? A comparison with Friedreich's ataxia.

An electrophysiologic and histologic study was performed on 18 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Sensory and motor conduction velocity (SCV, MCV) was measured along peripheral nerves in all patients, somatosensory (SSEP) and brainstem auditory evoked potentials (BAEP) were recorded in 13; cortical stimulation (CS) in 12, and sural nerve biopsy in 4 patients were also performed. The results as a whole allow a division of EOCA patients into 2 groups: with (7 patients) and without (11 patients) peripheral neuropathy. Among EOCA patients with neuropathy a differential diagnosis with Friedreich's disease patients was not possible according to BAEPs and CS, while SSEPs could differentiate 2 out 5 patients in whom they were performed.     

Portal-systemic encephalopathy: alterations in somatosensory and brainstem auditory evoked potentials

Median somatosensory and brainstem auditory evoked potentials (SEP and BAEP) were studied in 40 patients with liver cirrhosis consequent to chronic viral hepatitis. The patients were divided into 4 groups: group 1 with liver cirrhosis only, group 2 with hepatic failure (HF), group 3 with grade 1 or 2 hepatic encephalopathy (HE), and group 4 with grade 3 or 4 HE. The control group consisted of 10 age-matched normal subjects. The major changes occurred in the median cortical SEP late components (peaks after N20 and P25). From group 1 to group 4, there were progressive prolongation and sequential disappearance of the late components. Those changes in the cortical SEPs were reversible. The subcortical somatosensory and brainstem auditory conductions (SEP N13-N20 and BAEP I-V interpeak latencies) were slightly prolonged in all groups of patients. The present data indicate that SEP may be useful in detecting subclinical HE and in monitoring the clinical course of HE. The present data further indicate that chronic portal-systemic shunting in liver cirrhosis may result in a minimal impairment of cerebral function and sensory conduction in the CNS.     

Peripheral and central sensory nerve conduction in Charcot-Marie-Tooth disease and comparison with Friedreich's ataxia

Somatosensory evoked potentials were recorded in response to stimulation of the median nerve at the wrist and the elbow in 14 cases of Charcot-Marie-Tooth disease (CMTD). Cervical and cortical latencies were used to derive conduction times and velocities over peripheral and central segments of the pathway. Sensory conduction velocities between the wrist and the elbow were distributed bimodally (12-27 m/s and 36-70 m/s), but did not correspond with the bimodality of motor conduction velocity values in 4 cases. Three patients had severely slowed sensory conduction in one arm but only moderate slowing in the other. In the majority of cases sensory conduction was considerably faster from the elbow to the spinal cord than from the wrist to the elbow. This was most apparent in 2 young patients, suggesting that demyelination secondary to axonal degeneration may gradually progress from distal to proximal segments. Compared with a group of Friedreich's ataxia (FA) patients, almost all CMTD cases could be distinguished by a greater degree of peripheral conduction slowing (not significant in FA). In FA there was a much higher incidence of impaired conduction over central segments of the somatosensory pathway, although evidence of this was also seen in 5 CMTD cases. Three of the latter had presented with atypical symptoms suggestive of CNS involvement, and also had delayed visual evoked potentials.     

脑干听觉及体感诱发电位对重型颅脑损伤病人预后的判断

目的分析探讨脑干听觉诱发电位(BAEP)及体感诱发电位(SEP)与重型颅脑损伤病人预后的关系。方法应用诱发电位仪对85例重型颅脑损伤患者早期行BAEP及SEP检查,并进行动态监测。结果重复检查BAEP及SEP均正常者,预后良好;BAEP及SEP均异常者,预后极差,与其他几组比较均有显著性差异(P<0.05)。结论BAEP与SEP联合应用并重复检查,可以比较准确的评估重型颅脑损伤患者的预后。     

Ataxia and areflexia in SOAA

Fifteen patients with the classical syndrome of ophthalmoplegia, ataxia, and tendon areflexia (SOAA) were studied in an attempt to clarify the mechanisms of ataxia and myotatic hyporeflexia. All showed features of cerebellar rather than sensory ataxia. Peripheral nerve conduction studies, including F-waves, were normal in a majority of the patients, as was needle EMG. Low-amplitude compound sensory nerve potentials were seen in four patients only, and mild slowing of sensory conduction velocity in two. Three had abnormal blink reflex studies, suggestive of a central lesion in two, and another two showed a transient delay of N5 peak of brainstem auditory evoked potentials. Somatosensory evoked potentials were normal. Despite clinically depressed or absent tendon jerks, T-waves were elicited at normal latencies. These findings do not support the prevailing view that the neurological abnormalities in SOAA are due to involvement of sensory fibres in the peripheral nerves and dorsal roots. We suggest that lesions scattered in the brainstem tegmentum and in the cerebellar peduncles are responsible for the ataxia and the depressed tendon jerks.     

Multimodal evoked potentials in neuro-Behçet: a longitudinal study of two cases

Two neuro-Behçet patients have been studied, over a period of several months, by means of peroneal and median somatosensory- (SEP), brainstem auditory- (BAEP), and visual- (VEP) evoked potentials. In both patients, peroneal SEP showed evidence of a pathological reduction in the central conduction velocity without a related deep sensation impairment, while VEP changes were consistent with the visual disorders. Conversely, BAEP and median SEP findings did not show disease-related abnormalities. The observed anomalies were detectable irrespective of the clinical phase of the disease. Thus, evoked potential assessment is useful in providing objective evidence for evaluating and monitoring CNS damage in neuro-Behçet's syndrome.     

Evoked potentials in motor system diseases

We studied pattern-shift visual (PSVEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potentials in 38 unselected patients with motor system diseases (MSD) (28 sporadic, 10 familial). PSVEPs were normal in all patients, and BAEPs were normal in all except one with clinical hearing loss who had absent waves I and III and prolonged wave V latencies. Median and tibial SEPs revealed definite CNS conduction abnormalities in only 1 of 30 and 1 of 18 patients, respectively. In addition, four patients had peripheral and four had peripheral or central delays on tibial nerve testing. There were no or only small group differences in central conduction SEP, BAEP, and PSVEP values in patients with normal studies compared with controls. This study suggests that central conduction SEP, BAEP, or PSVEP abnormalities can rarely be attributed to MSD and that their presence in patients suspected of having this disorder should prompt a search for an alternative diagnosis.     

Electrophysiological studies in spinocerebellar ataxia type 6: a statistical approach

In spinocerebellar ataxia type 6 (SCA6), the cerebellum is predominantly affected, but several electrophysiological studies have revealed subclinical disorders other than cerebellar lesions. We conducted statistical analyses by comparing SCA6 patients and age-matched normal controls to asses whether electrophysiological abnormalities are directly associated with SCA6 because late onset of SCA6 may involve senile changes. We performed brain stem auditory evoked potentials (BAEP), visual evoked potentials, somatosensory evoked potentials and nerve conduction studies in 10 SCA6 patients. The BAEP latencies of wave I was prolonged and compound muscle action potentials of peroneal nerve and sensory nerve action potentials of sural nerve reduced in SCA6 patients. Our results suggest an existence of peripheral impairment in the auditory pathway and axonal neuropathy in SCA6.     

Changes of brainstem auditory and somatosensory evoked

Objective: to investigate the characteristics and clinical value of evoked potentials in late infantile form of metachromatic leukodystrophy. Methods: Brainstem auditory, and somatosensory evoked potentials were recorded in 6 patients, and compared with the results of CT scan. Results: All of the 6 patients had abnormal results of BAEP and MNSEP. The main abnormal parameters in BAEP were latency prolongation in wave I, inter-peak latency prolongation in Ⅰ-Ⅲ and Ⅰ-Ⅴ. The abnormal features of MNSEP were low amplitude and absence of wave N9, inter-Peak latency prolongation in Ng-N13 and N13-N20, but no significant change of N20 amplitude. The results also revealed that abnormal changes in BAEP and MNSEP were earlier than that in CT. Conclusion: The detection of BAEP and MNSEP in late infantile form of metachromatic leukodystrophy might early reveal the abnormality of conductive function in nervous system and might be a useful method in diagnosis.     

Multimodality evoked potentials in patients and carriers with adrenoleukodystrophy and adrenomyeloneuropathy

A combination of brain-stem auditory evoked potentials (BAEPs), short latency somatosensory evoked potentials (SEPs) and pattern reversal visual evoked potentials (VEPs), were studied in two patients with adrenoleukodystrophy (ALD) and one patient with adrenomyeloneuropathy (AMN), as well as in one female carrier of each of the respective diseases. Abnormalities in at least 1 of the 3 evoked potentials were found in every case, including the carriers of ALD and AMN. The two most common findings were prolongation of the I-V interval of the BAEP and the N13-N20 interval of the SEP. These abnormalities were recorded either alone or in combination in all 5 cases. This finding suggests delayed conduction time in the central sensory pathways in both diseases, probably due to demyelination. The remarkable result, which distinguished AMN from ALD, even in their respective carriers, was delay of the N9 latency of the SEP, indicating slowing in conduction velocity of the peripheral nerve. Multimodality evoked potentials are useful not only in raising the detection rate for abnormal findings, but also in providing additional information about the functional state of separate afferent pathways. It is also of value in detecting and differentiating the carriers of ALD and AMN.     

Clinical and electrophysiological findings in various hereditary sensory neuropathies]

An electrophysiological study, comprehensive of peripheral sensory and motor conduction velocity (SCV, MCV), motor cortical stimulation (CS), median nerve somatosensory evoked potentials (SSEPs), brainstem evoked potentials (BAEPs) and sural nerve biopsy, was performed on 100 hereditary ataxia patients: 48 with Friedreich's ataxia (FA), 18 with Early Onset Cerebellar Ataxia (EOCA) and 34 with Autosomal Dominant Cerebellar Ataxia (ADCA). An early "peripheral" and "central" sensory impairment was observed in FA probably due to axonal loss and not related to disease severity or duration. On the contrary, BAEP and CS findings suggested a progressive involvement of the auditory and motor pathways. The presence of a non progressive sensory neuropathy allowed a distinction of EOCA patients in two groups: with and without peripheral neuropathy. The clinical and genetic heterogeneity was confirmed by the variability of evoked potential results. The ADCA patients showed the mildest degree of electrophysiologic abnormalities with an involvement of the peripheral pathways, both sensory and motor, more frequent than the central ones.     

Central motor conduction to upper and lower limbs after magnetic stimulation of the brain and peripheral nerve abnormalities in 20 patients with Friedreich''s ataxia

Central motor conduction time (CMCT) to thenar and soleus muscles was measured after magnetic stimulation of the cortex in 20 cases of Friedreich's ataxia (FA) and was abnormal in all. CMCT values were related to disease duration and disability. The amplitude of CMAP after cortex stimulation was severely reduced in the most disabled patients. Reduction in amplitude of the nerve evoked potentials was related neither to disease duration nor grade of disability. These results suggest that clinical worsening in FA is mainly due to progressive central motor pathway involvement. CMCT study is a better index of disease progression than peripheral nerve examination. Abnormalities in CMCT may be the third electrophysiological diagnostic criterion in FA, after reduced amplitude of nerve action potentials and absent H reflex.     

颅内动脉瘤术中诱发电位监测的初步探讨

目的 初步探讨颅内动脉瘤手术中躯体感觉诱发电位、脑干听觉诱发电位及运动诱发电位的临床应用价值.方法 在16例动脉瘤手术中开展诱发电位监测,观察术中电生理信号改变与术后神经功能状态的关系.结果 11例术中未出现电生理信号异常改变,5例术中出现了异常信号,其中信号未能恢复正常的4例术后均出现新发神经功能障碍.结论 诱发电位监测可实时了解颅内动脉瘤手术中有无脑缺血所致的神经功能障碍,对指导手术及评估预后均有重要意义.

Abstract：

Objective To explore the application of intraoperative neuroelectrophysiological monitoring on somatosensory evoked potentials (SEP), brainstem auditory evoked potentials (BAEP) and motor evoked potentials (MEP) during intracranial aneurysm surgery.Methods SEP, BAEP or MEPs were monitored during operations on 16 patients with intracranial aneurysms.The relationship between the intraoperative changes of electrophysiological signals and the postoperative outcomes of neurological deficits was evaluated.Results 11 patients without abnormal intraoperative electrophysiological signal changes demonstrated no new neurological deficits after surgery.However, in the left 5 patients, abnormal changes of intraoperative electrophysiological signals were detected.Among these 5 patients, 4 with abnormal electrophysiological signals which were not recovered intraoperatively demonstrated new developed functional deficits immediately after surgery.Conclusion During intracranial aneurysm surgery, the monitoring on SEP, MEP and BAEP is beneficial not only to timely detecting neurological functional deficits resulted from intraoperative cerebral ischemia, but also to properly guiding surgical manipulation, and to reliably predicting postoperative outcome as well.