Mitochondrial abnormalities and intrafamilial variability of sural nerve biopsy findings in adrenomyeloneuropathy

Clinical and sural nerve biopsy findings in two brothers and their mother affected by adrenomyeloneuropathy/adrenoleukodystrophy (AMN/ALD) illustrate the variability of histopathological changes in this disorder. The number of diagnostic inclusions, i.e., trilaminar leaflets, varied considerably from case to case and showed no correlation to the extent of neurological symptoms. In addition, mitochondrial abnormalities (granular and filamentous inclusions and abnormal cristae), which have not previously been described in AMN/ALD, were detected. These alterations could be secondary to the peroxisomal defect and the increased amount of very long chain fatty acids or could be caused by a more generalized defect. Received: 13 November 1995 / Revised, accepted: 9 January 1996     

Clinical,biochemical and molecular genetic findings in a family with adrenomyeloneuropathy

A 42-year-old male patient presenting with clinical and biochemical evidence of adrenomyeloneuropathy (AMN) developed progressive spastic paraparesis and sensory ataxia from the age of 24. Biochemical studies showed elevated plasma concentration of saturated very-long-chain fatty acids (VLCFA). A nine-base pair deletion in exon one within the adrenoieukodystrophy (ALD) gene (967del9) was detected by mutation screening on the patient's genomic DNA. This mutation predicts the replacement of aspartic acid 194 by valine (D194V) and deletion of the three following amino acids in the deduced ALD protein sequence. The subsequent reading frame appears to be unaffected. Molecular genetic analysis in the patient's family allowed definitive identification of a heterozygous carrier of ALD/AMN and exclusion of the ALD/AMN carrier status for one possible heterozygous female.     

脑干及其附近手术诱发电位术中监护的研究

目的 探讨脑干及其周围手术损伤与脑干听觉诱发电位（ＢＡＥＰ）和体感诱发电位（ＳＥＰ）不同指标之间的关系,找出神经功能损伤第三的电生理指标。方法 对２３例脑干肿瘤病人进行手术中ＢＡＥＰ和ＳＥＰ连续监测。结果 脑干及其周围手术操作均可以引起ＢＡＥＰ、ＳＥＰ的改变。ＳＥＰ的Ｎ１３－Ｎ２０中枢传导时间（ＣＣＴ）和Ｎ２０潜伏期及波幅的变化和ＢＡＥＰＶ波潜伏期（ＰＬ）、Ⅲ－Ｖ、Ｉ－Ｖ峰间潜伏期（ＩＰＬ）的变化     

Evaluation of afferent pain pathways in adrenomyeloneuropathic patients

Objective

Patients with adrenomyeloneuropathy may have dysfunctions of visual, auditory, motor and somatosensory pathways. We thought on examining the nociceptive pathways by means of laser evoked potentials (LEPs), to obtain additional information on the pathophysiology of this condition.

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.     

多发性硬化患者的MRI及多种诱发电位研究

目的探讨磁共振成像(MRI)和诱发电位(EPs)在诊断多发性硬化中的价值。方法对68例多发性硬化患者的头颅MRI、脑干听觉诱发电位、视觉诱发电位以及体感诱发电位等指标进行回顾性分析和比较。结果多发性硬化患者的头颅MRI、脑干听觉诱发电位、视觉诱发电位以及体感诱发电位的异常率分别为91.2%(62/68)、80.9%(55/68)、82.4%(56/68)和77.9%(53/68),且均发现多发性硬化的亚临床病灶;两项或多项联合检查的异常率较单项检查的异常率增高,差异有统计学意义(P<0.01)。结论头颅MRI和诱发电位检查有助于临床早期确诊多发性硬化,联合应用可使其敏感性提高。     

多发性硬化患者前庭诱发肌源性电位的临床意义

目的研究多发性硬化(multiple sclerosis,MS)患者前庭诱发肌源性电位(vestibularevoked myogenic potentials,VEMPs)各参量的变化及临床意义,比较VEMPs与核磁共振、脑干听觉诱发电位对MS病变的检测能力。方法采用双耳短声刺激记录37例MS患者(有脑干症状21例、无脑干症状16例)和20名健康对照的VEMPs的潜伏期和振幅值,计算双侧在13ms左右出现的正波(p13)波幅潜伏期差值(Δp13)和振幅比(SR)。37例MS患者均做核磁共振成像,其中33例记录脑干听觉诱发电位。结果有脑干症状组和对照组相比,p13潜伏期显著延长[左侧为(13.84±2.57)ms和(12.20±1.10)ms,P<0.05;右侧为(14.69±2.96)ms和(12.10±2.60)ms,P<0.01],Δp13显著增大(1.63±1.82和1.00±1.44,P<0.01),而无脑干症状组差异无统计学意义。两组MS患者的p13-n23(在23ms左右出现的负波)振幅值与对照组相比均降低[左侧分别为(149.98±52.2)、(175.51±49.22)、(272.80±165.81)μV;右侧分别为(156.88±97.04)、(167.74±57.32)、(257.50±138.49)μV,P均<0.05],扩展的残疾功能量表评分与振幅有相关性(左侧r=0.45,右侧r=0.46,P均<0.05)。VEMPs与核磁共振相比,对病灶的检出率低(分别为33%与100%,P<0.05),与脑干听觉诱发电位相比差异无统计学意义。结论p13潜伏期及Δp13可作为判定MS前庭脊髓通路脱髓鞘的参考指标。VEMPs作为辅助诊断MS的一项新的诱发电位,对脑干病灶的诊断有一定临床参考意义。     

脊椎旁刺激法体感诱发电位在脊髓病变中的临床应用

目的 探讨脊椎旁刺激法体感诱发电位（SEPs）在脊髓病变患者中进行脊髓功能判断的临床应用价值，并将诱发电位结果与脊髓MRI结果进行比较，初步探讨该方法在脊髓病变中的生理定位价值。方法 应用脊椎旁刺激、头皮记录的直接SEPs法对脊髓病变患者进行SEPs测定及脊髓传导速度（SCCV）测定。结果 共有96例脊髓病变患者行脊椎旁刺激法SEPs及SCCV测定，男53例，女43例，年龄15-75岁，平均46．78岁。其中脊髓脱髓鞘病36例，脊髓亚急性联合变性26例，脊髓病19例，急性脊髓炎10例，脊髓压迫性疾病5例。96例脊髓病变患者均做脊椎旁刺激法SEPs检查，脊髓诱发电位及SCCV的异常率在各脊髓病变中阳性率均较高，总异常率为81．25％（78／96）。其中脊髓脱髓鞘病异常率75．00％（27／36），脊髓亚急性联合变性异常率88．46％（23／26），脊髓病19例中有15例异常，脊髓炎异常率10例中有8例异常，脊髓压迫症5例均异常。共有68例患者做脊髓MRI检查，其中42例MRI异常，26例MRI正常。42例MRI异常患者中35例诱发电位结果异常，26例MRI正常患者中21例诱发电位结果异常。结论 脊椎旁刺激法SEPs及SCCV的测定客观地记录了脊髓病变的异常电生理改变，其异常电生理改变可能会出现在脊髓结构改变及影像学改变之前，可为脊髓病变患者早期脊髓功能性改变提供比较可靠的客观诊断依据，尤其在脊髓MRI少有阳性所见的营养代谢性脊髓病中意义更大。本方法简单、无创、具有可重复性，可在临床中应用。     

首发精神分裂症患者的脑诱发电位研究

目的：观察首发精神分裂症患者的脑诱发电位变化特点。方法：使用32导脑诱发电位仪对48例首发精神分裂症患者和46例正常人进行听觉和视觉诱发电位检测。结果：首发精神分裂症患者的脑诱发电位变化特点为：①波形变异性大，以主波群为主，后节律成分活跃性降低；②除潜伏期AEP-P1延长外，潜伏期。AEP-P2、N2和潜伏期VEP-N1、P2、N2、P3均显著缩短；③AEP、VEP的波幅N1-P2、P2-N2、P2均降低；④左右半球对称；⑤女性AEP、VEP的波幅均显著高于男性。结论：脑诱发电位变化对精神分裂症的诊断具有参考意义。     

The effects of subcortical lesions on evoked potentials and spontaneous high frequency (gamma-band) oscillating potentials in rat auditory cortex

Functional subdivisions of auditory cortex in the rat were identified based on the distribution of temporal components of the mid-latency auditory evoked potential (MAEP) recorded with a multichannel epipial electrode array. Spontaneous data collected from the same location exhibited spindle-shaped bursts of oscillations in the gamma-band (20–40 Hz) whose location and spatial distribution were similar to that of the MAEP complex in that the bursts were localized to primary and secondary auditory cortex, the principle targets of thalamocortical projections. This suggested that the neural generators of these electrophysiological events may be similar. However, ablation of the medial geniculate nucleus (MG) of the thalamus revealed that while this nucleus is required for the generation of MAEPs, it is not required for the generation of spontaneous gamma-band oscillations. Ablation of subcortical cholinergic nuclei revealed that cholinergic input via the thalamus or the basal forebrain is not necessary for the generation of either MAEPs or spontaneous gamma-band oscillations recorded in this study. These results indicated that there may be networks of cells in sensory cortical areas endowed with an intrinsic capacity to oscillate independently of sensory or cholinergic input, but that may be modulated by this input.     

Somatosensory evoked potentials in patients with thalamic lesions

Summary Somatosensory evoked potentials (SEPs) were recorded in 20 patients with thalamic lesions confirmed by CT (10 with infarction, 10 with haemorrhage). The changes in SEP configuration are discussed in their relationship to clinical symptoms. Four types of SEP abnormality produced by thalamic lesion are distinguished: (1) FF type, (2) N20/P23 dissociation type, (3) N18/N20 false shift type, and (4) reduced early component type. It was shown that clinically similar lesions might produce different SEP patterns.     

Polysensory evoked potentials in rat parietotemporal cortex: combined auditory and somatosensory responses

A 64 channel microelectrode array was used to map auditory evoked potentials (AEP), somatosensory evoked potentials (SEP) as well as combined auditory and somatosensory evoked potentials (ASEP) from a 7 × mm² area in rat parietotemporal neocortex. Cytochrome oxidase (CO) stained sections of layer IV were obtained in the same animals to provide anatomical information underlying epicortical field potentials. Epicortical responses evoked by click or vibrissa stimuli replicated earlier findings from our laboratory, and appeared as a family of waveforms centered on primary auditory (AI) or somatosensory (SI) cortical areas as determined from CO histology. Selective microinjections of HRP to AI and SI further confirmed their specific sensory relay nuclei in the thalamus. A small polysensory area between AI and SI, responded uniquely with an enhanced negative sharp wave to combined auditory and somatosensory stimuli. HRP retrograde labeling revealed that the thalamocortical projections to this area were from the posterior nuclear group (Po) and medial division of the medial geniculate (MGm). These data establish close relationships between epicortical AEP, SEP, and especially ASEP and corresponding cortical structures and thalamocortical projections. The neurogenesis of unimodal and polysensory evoked potentials is discussed in terms of specific and non-specific systems.     

Effect of long-term swimming exercise on somatosensory evoked potentials in rats

The study investigated whether long-term swimming exercise prevents age-related changes in rat somatosensory evoked potentials (SEPs) and somatosensory cortex (SC) morphology. A total of 25 9-month-old rats were assigned to an exercise or control group. The exercise group swam 1 h/day five times weekly for 1 year. The results showed that long-term exercise prevented age-related changes in SEPs and SC morphology.     

遗传性小脑共济失调的多形式诱发电位研究

研究遗传性小脑共济失调的诱发电位变化。方法采用多种形式诱发电位，对３６例此类疾病的患者进行检测，并与３０～４０名健康者作对比。结果全部患者至少存在１种以上的诱发电位异常。磁刺激运动诱发电位（ＭＥＰ）、脑干听觉诱发电位（ＢＡＥＰ）及胫后神经与正中神经体感诱发电位（ｔＳＥＰ、ｍＳＥＰ）的异常率分别为８３．３％、８８．９％、８０．０％和６２．５％。不同类型小脑共济失调的诱发电位异常率不同，各型ＢＡＥＰ的异常率普遍较高，橄榄－桥脑－小脑萎缩患者的ＭＥＰ与遗传性痉挛性共济失调的ｔＳＥＰ异常率也很高。ＭＥＰ测试时，刺激皮质在患者中所记录到的双峰波、多相波以及波宽增加，表明皮质运动神经元的异常放电。结论多形式诱发电位改变应列为慢性小脑变性分类学上的诊断依据     

痛觉诱发电位示肌萎缩侧索硬化患者痛觉通路正常

目的 研究肌萎缩侧索硬化患者痛觉诱发电位的特点,评估其痛觉通路的传导.方法 肌萎缩侧索硬化患者60例,取卧位,应用接触性热痛诱发电位刺激器,直径27 mm(面积573 mm2),加热速度70℃/s.于54.5℃应用可调节脉冲,刺激部位为手背、前臂的掌侧面、第7颈椎棘突处(C7).记录仪器:Keypoint.net仪器.记录点为Cz和Pz.同时进行躯体感觉诱发电位检测,记录其波形及潜伏期.并对60名健康对照者进行相应研究.结果 肌萎缩侧索硬化患者接触性热痛诱发电位波形无异常,潜伏期分别为:手背刺激(561.2±28.6)ms,前臂掌侧刺激(540.1±39.2)ms,C7刺激(512.7±31.4)ms,与健康对照组[(558.7±30.2)、(536.6±23.5)、(501.8±26.0)ms]比较差异均无统计学意义(t=4.23、4.51、3.74,P＞0.05).其躯体感觉诱发电位各波潜伏期、波间期均正常.结论 肌萎缩侧索硬化患者接触性热痛诱发电位正常,提示其痛觉通路正常.     

Lack of adrenoleukodystrophy protein enhances oligodendrocyte disturbance and microglia activation in mice with combined <Emphasis Type="Italic">Abcd1</Emphasis>/<Emphasis Type="Italic">Mag</Emphasis> deficiency

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurometabolic disease associated with the accumulation of very long-chain fatty acids. Mutations in the ABCD1 gene encoding ALD protein (ALDP) cause this clinically heterogeneous disorder, ranging from adrenocortical insufficiency and neurodegeneration to severe cerebral inflammation and demyelination. ALDP-deficient mice replicate metabolic dysfunctions and develop late-onset axonopathy but lack histological signs of cerebral inflammation and demyelination. To test the hypothesis that subtle destabilization of myelin may initiate inflammatory demyelination in Abcd1 deficiency, we generated mice with the combined metabolic defect of X-ALD and the mild myelin abnormalities of myelin-associated glycoprotein (MAG) deficiency. A behavioural phenotype, impaired motor performance and tremor, developed in middle-aged Mag null mice, independent of Abcd1 genotype. Routine histology revealed no signs of inflammation or demyelination in the CNS, but immunohistochemical analyses of spinal cord neuropathology revealed microglia activation and axonal degeneration in Mag and Abcd1/Mag double-knockout (ko) and, less severe and of later onset, in Abcd1 mutants. While combined Abcd1/Mag deficiency showed an additive effect on microglia activation, axonal degeneration, quantified by accumulation of amyloid precursor protein (APP) in axonal spheroids, was not accelerated. Interestingly, abnormal APP reactivity was enhanced within compact myelin of Abcd1/Mag double-ko mice compared to single mutants already at 13 months. These results suggest that ALDP deficiency enhances metabolic distress in oligodendrocytes that are compromised a priori by destabilised myelin. Furthermore, the age at which this occurs precedes by far the onset of axonal degeneration in Abcd1-deficient mice, implying that oligodendrocyte/myelin disturbances may precede axonopathy in X-ALD.     

Normal postexercise facilitation and depression of motor evoked potentials in postpolio patients

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation in healthy subjects and postpolio patients. Subjects performed repeated sets of isometric exercise until the muscle fatigued. In both groups, the mean MEP amplitude immediately after each exercise set was approximately twice that of the baseline amplitude, indicating similar postexercise facilitation, and after fatigue was approximately half that of the baseline amplitude, indicating similar postexercise depression. We conclude that the intracortical component of central fatigue is normal in postpolio patients. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:948–950, 1998.     

Binaural vs. monaural auditory evoked potentials in rat neocortex

High spatial resolution epicortical recording techniques and numerical modeling were used to investigate laterality effects on the middle latency auditory evoked potential (MAEP) complex. Our data confirm previous reports that auditory stimulus laterality has a consistent effect on the amplitude, timing, and spatial distribution of the MAEP complex. The earliest temporal components (P1a, P1b and N1) show the greatest sensitivity, and are absent during ipsilateral stimulation. The later positive slow wave (P2) is present at the same amplitude during all stimulation conditions. Generation of the P2 appears to be independent of prior activation of areas 36 and 41 reflected in the early components, suggesting its generation by a more diffuse thalamocortical pathway, possibly from the medial division of the medial geniculate. Serial vs. parallel activation of rodent auditory cortex is discussed in the context of laterality-sensitive MAEP components.