Neurophysiologic follow-up of long-term dietary treatment in adult-onset adrenoleukodystrophy

OBJECTIVE: To monitor the effects of dietary treatment in adult-onset adrenoleukodystrophy (ALD) by means of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs). BACKGROUND: SEPs and MEPs have proved useful in revealing signs of progressively severe, central dying-back axonopathy in early stages of adult-onset ALD. METHODS: Eight patients with adult-onset ALD underwent clinical examination, brain and spine MRI, and SEP and MEP studies before and after 3 years of Lorenzo's oil dietary therapy. RESULTS: Before treatment, brain MRI was normal in five patients. Three of these patients had pure spinal SEP abnormalities and in the remaining two patients SEPs showed signs of involvement of both the spinal and cerebral somatosensory tracts. After treatment, the three patients with pure spinal abnormalities showed clinical and neurophysiologic worsening, whereas the two patients with a more advanced stage of disease (exhibited by SEPs) showed substantially unchanged clinical and neurophysiologic features. The patients with abnormal brain MRI at the onset of treatment showed clinical and neurophysiologic worsening. CONCLUSIONS: Lorenzo's oil therapy had no effect on patients with evidence of inflammatory brain lesions. Moreover, in patients without clear signs of inflammatory damage, this treatment does not modify significantly the natural course of the disease. However, because effective treatments should begin before the onset of severe neurologic symptoms, SEPs and MEPs should be considered to evaluate the effectiveness of other experimental treatments in the patient with a negative brain MRI.     

Cutaneous silent periods in intramedullary spinal cord lesions

OBJECTIVE: The neurophysiological assessment of intramedullary spinal cord lesions has been unsatisfactory. Previous studies in patients with syringomyelia suggest that testing of cutaneous silent periods (CSPs) may be useful to assess centromedullary lesions. METHODS: The authors studied nine patients with intramedullary spinal cord lesions of different etiologies. Eight patients with cervical lesions presented with hypalgesia, hypothermesthesia, or pain in at least one upper extremity; five of them had also upper limb weakness or sensory impairment. One patient with a thoracic lesion had normal upper limb function. The authors recorded CSPs in abductor pollicis brevis muscle following digit II and digit V stimulation. Somatosensory evoked potentials (SEPs) were obtained following median and tibial nerve stimulation. Motor evoked potentials (MEPs) were obtained in biceps brachii, abductor digiti minimi and tibialis anterior muscles following transcranial magnetic or electrical stimulation. RESULTS: CSP abnormalities were found in all patients with cervical lesions, but not in the patient with a thoracic lesion. Cortical median nerve SEPs had normal latencies in all patients, while tibial nerve SEPs, upper limb MEPs, and lower limb MEPs were delayed in five patients each. In one patient, abnormal CSP were the only neurophysiological finding. CSP abnormalities were associated with hypalgesia and hypothermesthesia in 95% of the studies. CONCLUSION: Upper extremity CSP testing is a sensitive neurophysiological technique for the assessment of cervical intramedullary lesions. In particular, abnormal CSPs are highly associated with spinothalamic dysfunction.     

Subcortical somatosensory evoked potentials after median nerve and posterior tibial nerve stimulation in high cervical cord compression of achondroplasia

Children with achondroplasia may have high cervical myelopathy from stenosis of the cranio-cervical junction resulting in neurological disability and an increased rate of sudden death. To detect myelopathy we recorded somatosensory evoked potentials after median nerve (MN) and posterior tibial nerve (PTN) stimulation in 77 patients with achondroplasia aged 0.3–17.8 years (mean 2.7 years). In addition to the conventional technique of recording the cortical components and the central conduction time (CCT) we employed non-cephalic and mastoid reference electrodes to record the subcortical waveforms N13b and P13 (MN-SEP) as well as P30 (PTN-SEP), respectively, which are generated near the cranio-cervical junction. The findings were related to the MRI results. Thirty-four patients had abnormal MRI findings including spinal cord compression (n = 28) and/or myelomalacia (n = 24) at or below the cranio-cervical junction. The sensitivity of the MN-SEPs was 0.74 including all abnormal upper cervical cord MRI findings (specificity 0.98), and the sensitivity was 0.79 (specificity 0.92) for cervical cord compression, respectively. The sensitivity of the PTN-SEPs was 0.52 (specificity 0.93) for all abnormal MRI findings and 0.59 (specificity 0.92) for cervical cord compression. The subcortical SEPs N13b and P13 as well as P30 were more sensitive than the conventional recordings. The MN-SEPs, notably the subcortical tracings, are useful for the detection of cervical myelopathy in children with achondroplasia. The PTN-SEPs are less sensitive. However, the tibial nerve SEPs might contribute additional information from the lumbar or thoracic spinal cord, which was, however, not tested in this study.     

Neurophysiological and radiological findings in myotonic dystrophy patients

Somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs) were recorded in 10 patients with myotonic dystrophy and in 20 sex and age-matched healthy controls. In all patients a brain MRI examination was also performed. In our results, the significantly longer absolute peak latencies of the SEPs and the abnormal increasing of the later components of the BAEPs suggest an involvement of the afferent sensory and central auditory pathways. Brain MRI showed white matter hyperintense lesions (WMHL) in eight patients (80%). No correlations were found between individual abnormal electrophysiological parameters or severity of WMHL and age, age at onset, disease duration or muscular impairment. The total number (SEP + BAEP) of electrophysiological abnormalities significantly correlated with muscular impairment ( p < 0.05) and MRI changes ( p < 0.05), suggesting a strict pathogenetic linkage between muscular and nervous system alterations in this disease.     

Neurophysiological studies in acute transverse myelitis

A systematic evaluation of anterior horn cell, motor and sensory pathways is possible by electromyography (EMG), motor (MEPs) and somatosensory (SEPs) evoked potentials, respectively, which may provide valuable information on acute transverse myelitis (ATM). In a prospective hospital-based study, EMG, MEP and SEP studies were carried out on admission and after 3 months in 39 patients with ATM. All the patients also underwent detailed clinical evaluation, and spinal magnetic resonance imaging (MRI) was performed in 28. Outcome was defined at the end of 3 months as poor, partial or complete recovery on the basis of functional status. Spinal MRI revealed hyperintense signal changes in T2 extending for two segments to the entire spinal cord. Central motor conduction time to tibialis anterior (CMCT-TA) was more frequently abnormal (90%), followed by tibial SEP (77%). CMCT to abductor digiti minimi (ADM) was abnormal in 30% and median SEP in 15% of patients. Evidence of denervation on EMG was present in 51% of patients. The CMCT-TA improved in 48% patients and tibial SEP in 32%. Median SEP improved in all patients, and CMCT-ADM remained prolonged in two. At 3 months 2 patients had died, and 18 had poor, 10 partial and 9 complete recovery. CMCT was correlated with miscle power, tone, reflec and MRI changes. Patients' outcome of was correlated with CMCT, SEP and EMG. These results are consistent with pronounced involvement of dorsal region of spinal cord in ATM. MEP is more frequently abnormal than SEP. Received: 31 August 1999 / Received in revised form: 12 June 2000 / Accepted: 28 June 2000     

Serial changes in motor and somatosensory evoked potentials in putaminal haemorrhage

Little is known about evoked potential changes in putaminal haemorrhage. In this study, somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) have been serially evaluated and their role in the prognosis of putaminal haemorrhage is now reported. Nineteen patients with CT- or MRI-proven putaminal haemorrhage were examined after a mean duration of 13 days (range 2–30); there were 4 females and 9 males, ranging in age between 25 and 70 years. The haematomas were of medium size in 13 and large or small in 3 patients each. The changes in the clinical picture and the SEPs and MEPs were evaluated on admission, and after 30 and 90 days. Central motor conduction time (CMCT) could not be recorded in 13, but was prolonged in 2 and normal in 4 patients. Median SEPs revealed the absence of near field potentials in 11 and prolongation of N9–N20 conduction time in 1 patient. In the follow-up period MEP and SEP abnormalities only changed in 5 patients; MEPs changed in 4 and SEPs in 2. The period of normalisation of MEPs ranged between 1 and 6 months. CMCT correlated with motor and N9–N20 conduction time with sensory impairment. Eight patients had poor, 6 partial and 5 complete recovery. Power, sensation, CMCT, and size and location of haematoma made positive contributions to recovery.     

Evoked potential study in facio-scapulo humeral muscular dystrophy

Nerve conduction velocities (NCVs), somatosensory (SEPs) and auditory evoked potentials (BAEPs) were recorded in 9 patients with facio-scapulo-humeral dystrophy (FSHD) and in 20 age-matched controls. In FSHD patients a significant increase of the nerve distal sensory latencies and of the absolute SEP latencies revealed a subclinical involvement of the afferent sensory pathways, as well as the abnormal slowing of the later components of the BAEPs, pointed to a central auditory dysfunction. Moreover all patients underwent brain MRI that showed the presence of white matter hyperintense lesions in 4 of them (44%). No correlations were found between individual or total number of SEP and BAEP abnormal electrophysiological parameters and severity of WMHL, age, age at onset, duration of the disease or muscular impairment. These findings make the interpretation and pathophysiology of the nervous damage in FSHD rather uncertain. More studies are required to better define the aspects of neurogenic involvement in this type of muscular dystrophy.     

Neurophysiological testing in anorectal disorders

The neurophysiological techniques currently available to evaluate anorectal disorders include concentric needle electromyography (EMG) of the external anal sphincter, anal nerve terminal motor latency (TML) measurement in response to transrectal electrical stimulation or sacral magnetic stimulation, motor evoked potentials (MEPs) of the anal sphincter to transcranial magnetic cortical stimulation, cortical recording of somatosensory evoked potentials (SEPs) to anal nerve stimulation, quantification of electrical or thermal sensory thresholds (QSTs) within the anal canal, sacral anal reflex (SAR) latency measurement in response to pudendal nerve or perianal stimulation, and perianal recording of sympathetic skin responses (SSRs). In most cases, a comprehensive approach using several tests is helpful for diagnosis: needle EMG signs of sphincter denervation or prolonged TML give evidence for anal motor nerve lesion; SEP/QST or SSR abnormalities can suggest sensory or autonomic neuropathy; and in the absence of peripheral nerve disorder, MEPs, SEPs, SSRs, and SARs can assist in demonstrating and localizing spinal or supraspinal disease. Such techniques are complementary to other methods of investigation, such as pelvic floor imaging and anorectal manometry, to establish the diagnosis and guide therapeutic management of neurogenic anorectal disorders.     

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.

Motor responses evoked by magnetic brain stimulation in Huntington's disease.

In 34 patients with manifest Huntington's disease (HD), and in 21 first-degree offspring without clinical signs or symptoms, the sizes, central motor latencies (CMLs) and variation in latencies of EMG responses (MEPs) following transcranial magnetic brain stimulation were studied in muscles of the upper and lower extremities. In subgroups of patients and their offspring median and tibial nerve somatosensory evoked potentials (SEPs) and electrically elicited long-loop reflexes (LLRs) in hand muscles were also investigated. Increased MEP thresholds were observed in 10% of the HD offspring, while CML, latency variability and MEP amplitudes always lay within normal range. In contrast, SEPs were abnormal in 33%. In HD patients MEPs were found to be abnormal in up to 72% of patients when all available response parameters were taken into consideration. MEP abnormalities correlated with the duration of motor symptoms and the severity of choreic motor activity. When both MEPs and SEPs were evaluated, abnormalities could be detected in 91% of all HD patients. We suggest that abnormal MEPs might reflect an altered excitability of the cortico-spinal system as a consequence of basal ganglia dysfunction, rather than a structural damage of the investigated descending pathways. To localize the pathological mechanism responsible for altered LLRs, a "loop analysis" was performed by recording LLRs, MEPs and SEPs in the same patients. Alterations of LLRs correlated best with abnormal SEPs and might therefore be explained by reduced somatosensory input to the motor cortex.     

Segmental dysfunction of the cervical cord revealed by abnormalities of the spinal N13 potential in cervical spondylotic myelopathy.

We studied somatosensory potentials (SEPs) evoked by stimulation of radial, median, and ulnar nerves in 11 patients with MRI evidence of cervical spondylosis. All patients presented with progressive spastic paraparesis that was either isolated or associated with lower motor neuron signs in the upper limbs, with preserved joint, touch, pain, and temperature sensations in the four limbs. In all patients, scalp SEPs reflecting the activity of the dorsal column system up to the parietal cortex were normal while segmental cervical cord dysfunction was manifested by an abnormal spinal N13 potential in 95% of radial, 90% of median, and 54% of ulnar nerve SEPs. These subclinical abnormalities of the spinal N13 SEP probably result from reduced blood supply due to compression of the anterior spinal artery in patients with cervical spondylotic myelopathy.     

SEPs and CNS magnetic stimulation in syringomyelia.

Somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) to transcranial and spinal stimulation from upper and lower limb muscles were elicited in 13 patients with syringomyelia. Seven had an associated Chiari type I anomaly. Diagnosis was confirmed by MRI. In 5 cases, SEPs and MEPs were performed before and after surgical treatment. Prolonged central motor conduction times or absent motor responses in upper or lower limbs were found in most patients. The greatest number of abnormalities was disclosed by measurement of CMCT followed by SEPs after tibial nerve stimulation. Two of 5 cases undergoing surgery improved clinically and showed reduction in CMCT after surgical treatment. Our study shows that MEPs were useful in the evaluation of neurophysiological status in syringomyelia patients, helping to estimate anterolateral spinal cord function.     

Somatosensory evoked potentials after multisegmental upper limb stimulation in diagnosis of cervical spondylotic myelopathy.

Radial, median, and ulnar nerve somatosensory evoked potentials (SEPs) were recorded, with non-cephalic reference montage, in 38 patients with clinical signs of cervical myelopathy and MRI evidence of spondylotic compression of the cervical cord. Upper limb SEPs are useful in spondylotic myelopathy because SEPs were abnormal in all patients for at least one of the stimulated nerves and SEP abnormalities were bilateral in all patients but one. Reduction of the amplitude of the N13 potential indicating a segmental dysfunction of the cervical cord was the most frequent abnormality; it occurred in 93.4%, 84.2%, and 64.5% of radial, median, and ulnar nerve SEPs respectively. A second finding was that the P14 far-field potential was more sensitive than the cortical N20 potential to slowing of conduction in the dorsal column fibres. The high percentage of N13 abnormalities in the radial and median rather than in the ulnar nerve SEPs correlated well with the radiological compression level, mainly involving the C5-C6 vertebral segments. Therefore the recording of the N13 response is a reliable diagnostic tool in patients with cervical spondylotic myelopathy and P14 abnormalities, though less frequent, can be useful in assessing subclinical dorsal column dysfunction.     

Somatosensory and visual evoked potentials in children with cerebral palsy: Correlations and discrepancies with MRI findings and clinical picture

Purpose: To determine if there is any association between the findings of visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs), and magnetic resonance imaging (MRI) findings with the neurodevelopment and severity in children with cerebral palsy (CP). Methods: The present study included 15 children with spastic diplegic CP and five children with spastic hemiplegic CP and 42 healthy children as controls. The number of the controls was two-times greater than the study group to increase statistical power of this study. VEPs and SEPs were recorded in the CP children and compared with healthy controls. All MR scans were obtained using a 1.5 T MR scanner. Results: A significant difference was found in the latencies P100 (VEP) between the CP and controls. No correlations between increased P100 latencies and asphyxia, prematurity, the CP severity, MRI findings and mental retardation were noted. A significant difference in N13–N20 conductions (SEPs) between the subjects with CP and the control group was found. SEPs were positively correlated with mental retardation in CP children. The brain lesions in MRI showed a significant correlation with the CP severity scores and mental retardation. Conclusion: The differences in VEPs and SEPs were determined between CP children and healthy children. The MRI findings were positively correlated with the CP severity and mental retardation.     

Spinal arteriovenous malformations: Clinical and neurophysiological findings

Eighteen patients with dural arteriovenous fistulas or intradural arteriovenous malformations underwent clinical and neurophysiological examination. Bladder disturbances, pain, sensory abnormalities and involvement of both upper and lower motor neurons were commonly observed. Abnormal findings were obtained both in electromyography (11/18) and somatosensory evoked potentials (16/18). The motor evoked potentials were abnormal in all but one patient and showed a prolonged central (n = 14) or peripheral motor conduction time (n = 6). In three cases both values were prolonged. The results of nerve conduction studies in the patients with prolonged peripheral motor conduction times were normal. These neurophysiological findings may indicate root involvement in some patients, probably due to venous congestion and consequent hypoxia, as there were no signs of root compression on neuroradiological evaluation in any of these six patients. Motor evoked potentials may provide an additional clue to the diagnosis, although patients with spinal stenosis or motor neuron disease may present with similar findings.     

Sensory physiology assessed by evoked potentials in survivors of poliomyelitis

Evidence suggests that sensory loss may occur in a proportion of patients affected by poliomyelitis. We hypothesize that sensory problems may be a lasting sequela in some polio survivors. Sensory pathways in polio survivors were evaluated clinically and electrophysiologically using sensory evoked potentials (SEPs). Patients with sensory deficits or abnormal SEPs were further evaluated by magnetic resonance imaging (MRI). Twenty-two patients were studied. The mean age was 64.7 years (age range: 56-81 years). Clinically, sensory impairments were found in 4 patients. Upper limb SEPs were normal. Lower limb SEPs were abnormal in 10 patients. In 1 patient, clinical and electrographic findings correlated with a patch of atrophy in the spinal cord, as shown by MRI. Sensory derangements may be found in a proportion of aging polio survivors. SEP studies may add sensitivity when evaluating sensory function in this cohort. It remains unclear whether these sensory abnormalities are related to remote poliomyelitis. Further studies are necessary.     

Spinal segmental somatosensory evoked potentials in lumbosacral radiculopathies

We studied 21 patients with lumbosacral radiculopathy with segmental somatosensory evoked potentials (SEPs) recorded over both spine and scalp following saphenous, superficial peroneal, and sural nerve stimulation. Spinal SEPs were abnormal in 10 patients. In 3 patients, SEPs detected abnormalities not seen on EMG examination. With 1 exception, all anatomic levels of SEP abnormalities matched that of radiographic, EMG, or clinical abnormalities. SEPs were abnormal in 41% of nerve roots shown to be involved by other techniques. SEPs added to the clinical evaluation in 4 patients, but were less accurate than a combination of EMG and radiography in indicating the extent of nerve root involvement. We conclude that spinal SEPs following segmental sensory stimulation are useful in the evaluation of lumbosacral radiculopathies and complement information provided by the EMG. In contrast, scalp-recorded segmental SEPs rarely provide additional useful clinical information.     

Assessment of intraspinal and intracranial conduction by P30 and P39 tibial nerve somatosensory evoked potentials in cervical cord, brainstem, and hemispheric lesions.

In routine recordings of tibial nerve somatosensory evoked potentials (SEPs), a global central conduction time is evaluated by measuring the interval between the segmental spinal N22 potential, recorded in the lumbar region, and the cortical P39 potential. In this study, we tested the reliability of the scalp far-field P30 potential, which originates in the vicinity of the cervico-medullary junction, in order to evaluate separately intraspinal and intracranial conduction in normal subjects and patients with cervical cord and intracranial lesions. P30 and cortical P39 potentials were studied in 23 healthy subjects and in 70 patients with cervical cord (n = 47), brainstem (n = 11) or hemispheric lesions (n = 12) selected on the basis of neuroimaging--computed tomography (CT) or magnetic resonance (MR)--findings. Median nerve SEPs were also recorded in all patients. Of the several montages tested to obtain the P30 potential, the Fpz-Cv6 derivation gave the highest signal-to-noise ratio; it permitted to obtain a P30 potential that peaked at 29.2 +/- 1.6 ms in all normal subjects. P30 abnormalities were observed only in patients with cervical or cervico-medullary lesions; these were associated with a normal P39 in only two of 33 abnormal recordings. Conversely, P30 was consistently normal in lesions situated above the cervico-medullary junction whether associated with normal, delayed, or reduced P39. P30 abnormalities were subclinical in 42% of abnormal recordings. All patients with normal tibial and median nerve SEPs on both sides had normal touch, joint, and vibration sensation in the four limbs. There was a strong correlation between tibial nerve P30 and median nerve P14 data in the whole series of patients; both potentials behaved similarly in all cases of intracranial supramedullary lesions. Combined abnormalities of P30 and P39 potentials thus indicate that conduction is impaired at the spinal level and proved to be particularly informative for detecting spinal cord dysfunction in patients with neuroimaging evidence of a narrowed cervical canal. Recording of abnormal N13, P14, or P30 potentials provided evidence of a cervical cord dysfunction in 66% of patients who had a suspected spondylotic myelopathy. Recording of tibial nerve P30 potential has proven to give reliable and useful information when a separate assessment of intraspinal and intracranial somatosensory conduction is needed; it merits inclusion, as does the upper limb N13 potential, in the evaluation of patients whose MR image indicates cervical canal narrowing.     

Posterior tibial and sural nerve somatosensory evoked potentials in dystrophia myotonica

Somatosensory evoked potentials (SEPs) were recorded in a group of 18 patients with dystrophia myotonica and in 28 control subjects after stimulating the right and left posterior tibial (SEP-PT) and sural (SEP-S) nerves at the ankles. Recording electrodes were placed in the popliteal fossae, overlying the L3 spinal vertebrae, and at the appropriate scalp sites. In all control subjects and dystrophia myotonica subjects SEP-PT latencies were shorter than equivalent SEP-S latencies, probably reflecting conduction along group I muscle afferents and along slower conducting cutaneous afferents, respectively. Intergroup comparisons revealed prolonged absolute and interpeak latencies in the dystrophia myotonica group, showing both peripheral and central somatosensory pathway involvement. Individual abnormal latencies which exceeded the control group mean plus 3 standard deviations were found in 66% of the dystrophia myotonica group, mainly due to prolonged peripheral conduction times. Results pointed to the concomitant involvement of both the posterior tibial and sural nerve somatosensory pathways in dystrophia myotonica.     

Somatosensory evoked potentials after posterior tibial nerve stimulation in focal spinal cord diseases.

We investigated the somatosensory evoked potentials (SEPs) produced by posterior tibial nerve (PTN) stimulation in 8 infants and children with focal spinal cord disorders. The spinal responses of the PTN-SEPs were considered to assist in the localization of spinal lesions because their abnormalities were consistent with the neurologic and/or radiologic findings in all 6 examinations that revealed abnormal spinal SEPs. The cortical responses correlated significantly with proprioception in the lower limbs because proprioception was only disturbed when the cortical SEPs were absent (3 examinations). When both the spinal and cortical responses were abnormal, the spinal lesion probably involved the dorsal column so extensively that it completely interrupted the afferent impulses. In contrast, when SEP studies demonstrated abnormal spinal and normal cortical SEPs (3 examinations), the dorsal column involvement was probably less severe; therefore, both the spinal and cortical responses provided useful information regarding afferent conduction in the dorsal column. PTN-SEPs appear to have the potential to be of value in the diagnosis of focal spinal disease, especially in infants and young children who cannot cooperate with detailed neurologic examinations.