Upper motor neuron assessment in amyotrophic lateral sclerosis using the patellar tendon reflex and motor-evoked potentials to the lower limbs.

Amyotrophic lateral sclerosis (ALS) diagnosis relies on signs of progressive damage to both lower motoneuron (LMN), given by clinical examination and electromyography (EMG), and upper motoneuron (UMN), given by clinical examination only. Recognition of UMN involvement, however, is still difficult, so that diagnostic delay often remains too long. Shortening the time to clinical and genetic diagnosis is essential in order to provide accurate information to patients and families, avoid time-consuming investigations and for appropriate care management. This study investigates whether combined patellar tendon reflex recording with motor-evoked potentials to the lower limbs (T-MEP-LL) is relevant to assess corticospinal function in ALS, so that it might serve as a tool improving diagnosis. T-MEP-LL were recorded in 135 patients with suspected motor neuron disease (MND) from February 2010 to March 2021. The sensitivity, specificity, and ability to improve diagnosis when added to Awaji and Gold Coast criteria were determined. The main finding of the study is that T-MEP-LL can detect UMN dysfunction with a 70% sensitivity and 63% specificity when UMN clinical signs are lacking. The sensitivity reaches 82% when considering all MND patients. Moreover, at first evaluation, using T-MEP-LL to quantify reflex briskness and to measure central conduction time, can improve the diagnostic accuracy. T-MEP-LL is easy to perform and does not need any electrical stimulation, making the test rapid, and painless. By the simultaneous quantification of both UMN and LMN system, it could also help to identify different phenotype with more accuracy than clinical examination in this broad-spectrum pathology. The question whether T-MEP-LL could further be a real biomarker need further prospective studies.

Ulnar neuropathy at the elbow: Reappraisal of the wrist-upper arm latency difference between ulnar and median nerves.

OBJECTIVES: To evaluate the sensitivity and specificity of the latency difference (DLat) between ulnar and median nerves of the arm after stimulation at the wrist; one of the easiest techniques proposed for recognizing ulnar neuropathy at the elbow (UNE). As latency difference is not a standardized technique, we set up a multicenter study to recruit large numbers of normal subjects and patients with UNE or generalized neuropathy. METHODS: Six centers participated in the study with data obtained from three groups of participants, controls (CTRLs), patients with UNE and patients with generalized neuropathy (GNP). We first verified the anatomical superposition of the ulnar and median nerves in cadaver examination. The optimal recording site for these two nerves was found to be 10 cm above the medial epicondyle. We then standardized the position of the arm with full extension of the elbow and stimulated first the median and then the ulnar nerves at the wrist. CTRLs were examined on both arms at two consecutive visits. RESULTS: We recorded 32 idiopathic UNE cases, 44 GNP patients and 62 controls. We demonstrated that a DLat cut-off value of 0.69 ms brings a sensitivity of 0.86 and specificity of 0.89 to discriminate CTRLs from UNE. We also validated that intra-examiner reproducibility was good. CONCLUSION: We report a lower normal value for DLat than reported in several non-standardized studies and CTRL and UNE groups have clearly separated DLat values. SIGNIFICANCE: Due to its high sensitivity, our standardized technique could be used as a first-line diagnostic tool when UNE is suspected.

Early-onset or rapidly progressive scoliosis in children: check the eyes!

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare autosomal recessive disorder characterized by the absence of conjugate horizontal eye movements, and progressive scoliosis developing in childhood and adolescence, caused by mutations in the ROBO3 gene which has an important role in axonal guidance and neuronal migration. We describe two female children aged 12 years and 18 months, with progressive scoliosis, in whom the neurological examination showed absent conjugate horizontal eye movements, but preserved vertical gaze and convergence. Cerebral Magnetic resonance imaging findings included pontine hypoplasia, absent facial colliculi, butterfly configuration of the medulla and a deep midline pontine cleft, while Diffusion tensor imaging (DTI) maps showed the absence of decussating ponto-cerebellar fibers and superior cerebellar peduncles. Somatosensory and motor evoked potential studies demonstrated ipsilateral sensory and motor responses. The diagnosis was confirmed by the identification of bi-allelic mutations in the ROBO3 gene.

Epilepsy and cerebellar ataxia associated with anti-glutamic acid decarboxylase antibodies.

Anti-glutamic acid decarboxylase (GAD) antibodies are described in stiff-person syndrome and also in other neurological syndromes, including cerebellar ataxia and epilepsy. This paper reports the case of a patient who had chronic focal epilepsy, upbeat nystagmus and cerebellar ataxia, associated with a polyautoimmune response including anti-GAD antibodies. Both gait and nystagmus improved markedly after immunosuppressive treatment with corticosteroids and azathioprine. After the introduction of benzodiazepines, previously refractory seizures were completely controlled. Anti-GAD antibodies should be actively sought out in pharmacoresistant epilepsy, particularly if other neurological abnormalities are present. Combined treatment with immunosuppressants and γhydroxybutyric acidergic agents may be highly effective.

Corneal nerves alterations in various types of systemic polyneuropathy, identified by in vivo confocal microscopy.

BACKGROUND: In vivo confocal microscopy (IVCM) is a newly developed application to assess corneal nerve morphology. The purpose of the study is to evaluate the role of IVCM in the assessment of various types of polyneuropathy, and to define alterations of corneal nerves in such conditions. PATIENTS AND METHODS: Eighteen patients with various types of polyneuropathy were characterized by clinical neurological and ophthalmic examinations, as well as by electroneuromyography (ENMG). Full thickness IVCM of corneal nerves was carried out on all patients and 15 age-matched eyes using Heidelberg Retina Tomograph II (HRT II). The subbasal nerve plexus were statistically analysed regarding long nerve fiber density, nerve branch density, nerve thickness, nerve bead number and nerve tortuosity. RESULTS: In subbasal nerve plexus, the following three parameters were significantly reduced in patients with polyneuropathy compared to controls: long nerve fibre density (p < 0.01), nerve branch density (p < 0.001), and nerve bead number (p = 0.001). In addition, the average grade of nerve tortuosity was 2.87 +/- 0.97 in the polyneuropathic group and 1.17 +/- 0.68 in the control group (p < 0.0001). CONCLUSIONS: IVCM allows a non-invasive, in vivo study of corneal nerves with high resolution. It therefore appears invaluable in clinical investigations. IVCM appears to be valuable in a large variety of polyneuropathic conditions.

Epilepsy and cerebellar ataxia associated with anti-glutamic acid decarboxylase antibodies.

Anti-glutamic acid decarboxylase (GAD) antibodies are described in stiff-person syndrome and also in other neurological syndromes, including cerebellar ataxia and epilepsy. This paper reports the case of a patient who had chronic focal epilepsy, upbeat nystagmus and cerebellar ataxia, associated with a polyautoimmune response including anti-GAD antibodies. Both gait and nystagmus improved markedly after immunosuppressive treatment with corticosteroids and azathioprine. After the introduction of benzodiazepines, previously refractory seizures were completely controlled. Anti-GAD antibodies should be actively sought out in pharmacoresistant epilepsy, particularly if other neurological abnormalities are present. Combined treatment with immunosuppressants and gammahydroxybutyric acidergic agents may be highly effective.

[Lombosacral radiculopathy (L3-S1) and specificity of multifidus EMG]. / Radiculopathies lombosacrées (L3-S1) et spécificité de l'EMG du muscle multifidus.

AIMS OF THE STUDY: This prospective study tried to establish, in a group of patients with lombosacral radiculopathy, whether the electromyography of the multifidus muscles following the "Paraspinal Mapping" described by Haig and colleagues (1991, 1993, 1995, 1997) allows to specify the exact level of the radiculopathy. MATERIAL AND METHODS: Twenty-three patients with symptoms of mono or pluriradiculopathy were submitted to an EMG of the lower limbs and multifidus muscles at different levels in accordance to the "Paraspinal Mapping" cartography. RESULTS AND CONCLUSION: No patient had signs of acute denervation in the multifidus muscles that corresponded exclusively to the suspected levels as determined by clinical and radiological examinations. No patient had signs of acute denervation in the multifidus muscles without associated signs in the lower limb muscles. Conversely, four patients had signs of acute denervation in the lower limb muscles without any signs in the multifidus muscles. In our small series, the EMG of the multifidus muscles was neither sensitive nor specific and did not allow by itself topographical diagnosis.

Central motor conduction differs between acute relapsing-remitting and chronic progressive multiple sclerosis.

OBJECTIVE: To characterize central motor conduction in relation to the clinical deficits and to the disease duration in 90 patients with acute relapsing-remitting MS (RR-MS) and in 51 patients with chronic primary or secondary progressive MS (P-MS). METHODS: The triple stimulation technique (TST) was used to quantify the central motor conduction failure (expressed by the TST amplitude ratio) and conventional motor evoked potentials (MEPs) were used to measure the central motor conduction time (CMCT). RESULTS: The TST amplitude ratio was reduced in presence of a clinical motor deficit (p=0.02 for RR-MS, p<0.01 for P-MS), but did not significantly differ in RR-MS and P-MS (p>0.05) when patients with similar clinical motor deficit were compared. The CMCT was not related to the clinical motor deficit in both RR-MS and P-MS. However, the CMCT was markedly prolonged in P-MS, when patients with similar clinical motor deficit and with similar disease duration were compared (p<0.01). The differences were not attributable to differential involvement of the spinal cord, which was similar in RR-MS and P-MS. CONCLUSIONS: Our results disclose differences between the central motor conduction in RR-MS and P-MS that are not related to disease severity, spinal cord involvement or disease duration.

Endplate dysfunction causing respiratory failure in a patient with prior paralytic poliomyelitis.

A 56-year-old man with late amyotrophic sequelae from poliomyelitis experienced progressive dyspnoea requiring intubation and artificial ventilation in the intensive care unit. Repetitive stimulation studies showed a marked decrement of the trapezius muscle response reversible with edrophonium. Ventilatory function considerably and lastingly improved under anticholinesterase treatment. In the absence of biological evidence for autoimmune myasthenia gravis, it is suggested that a mechanism implying endplate dysfunction related to postpolio syndrome. Repetitive stimulation procedure should be considered in postpolio syndrome patients as some of them may benefit from anticholinesterase treatment.

The triple stimulation technique to study central motor conduction to the lower limbs.

OBJECTIVE: To quantify the percentage of motor units of a foot muscle that can be activated by transcranial magnetic stimulation (TMS) in normal subjects and patients. METHODS: We adapted the recently described triple stimulation technique (TST) for recordings from abductor hallucis (AH). Conventional motor evoked potentials (MEPs) of this muscle are usually small and variable in shape, because of an important temporal desynchronization of the TMS induced spinal motor neuron discharges. The TST allows 'resynchronization' of these discharges and thereby a quantification of the proportion of motor units activated by TMS. The lower limb (LL-) TST was applied to 33 sides of 18 normal subjects and 51 sides of 46 patients with multiple sclerosis, amyotrophic lateral sclerosis, or spinal cord disorders. RESULTS: In healthy subjects, the LL-TST demonstrated that TMS achieves activation of virtually all motor neurons supplying the AH. In 33 of 51 patient sides, abnormal LL-TST responses suggested corticospinal conduction failures of various degrees. The LL-TST was 2.54 times more sensitive to detect central conduction failures than the conventional LL-MEPs. Combining the LL-TST with TST of the upper limbs further increased the sensitivity to detect a conduction failure by 1.50 times. CONCLUSION: The LL-TST markedly improves the examination of corticospinal pathways.

Quantification of upper motor neuron loss in amyotrophic lateral sclerosis.

OBJECTIVE: To quantitatively estimate upper motor neuron (UMN) loss in ALS. METHODS: We used the recently developed triple stimulation technique (TST) to study corticospinal conduction to 86 abductor digiti minimi muscles of 48 ALS patients. This method employs a collision technique to estimate the proportion of motor units activated by a transcranial magnetic stimulus. At the same time, it yields an estimate of lower motor neuron (LMN) integrity. RESULTS: The TST disclosed and quantified central conduction failures attributable to UMN loss in 38 sides of 24 patients (subclinical in 15 sides), whereas conventional motor evoked potentials detected abnormalities in only 18 sides of 12 patients (subclinical in two sides). The increased sensitivity of the TST to detect UMN dysfunction was particularly observed in early cases. Increased central motor conduction times (CMCT) occurred exclusively in sides with conduction failure. In sides with clinical UMN syndromes, the TST response size (but not the CMCT) correlated with the muscle weakness. In sides with clinical LMN syndromes, the size of the peripherally evoked compound muscle action potentials correlated with the muscle weakness. CONCLUSION: The TST is a sensitive method to detect UMN dysfunction in ALS. It allows a quantitative estimate of the UMN loss, which is related to the functional deficit. Therefore, the TST has a considerable impact on diagnostic certainty in many patients. It will be suited to follow the disease progression and therapeutic trials.

Amyotrophic lateral sclerosis versus cervical spondylotic myelopathy: a study using transcranial magnetic stimulation with recordings from the trapezius and limb muscles.

OBJECTIVE: We report an electrophysiological method to differentiate amyotrophic lateral sclerosis (ALS) from cervical spondylotic myelopathy (CSM). METHODS: Motor evoked potentials (MEPs) by transcranial magnetic stimulation were investigated in patients with ALS (n=10) and CSM (n=9). In addition to limb MEPs using the triple stimulation technique (TST) at upper limbs, MEPs recorded from trapezius muscles were compared with those obtained from 23 normal subjects. The parameters studied were: central motor conduction time, amplitude ratio and, for the trapezius, the interside asymmetry. RESULTS: Whereas limb MEPs were abnormal in most ALS and CSM patients (17/19), trapezius MEPs were abnormal in all ALS patients, and normal in 8 out of 9 CSM patients. CONCLUSION: Recording of trapezius MEPs is a valuable addition to the limb MEPs study, since it distinguishes ALS from SCM in most patients.

Rapid cortical motor output map changes assessed by the triple stimulation technique.

The amplitudes of motor evoked potentials (MEPs) were mapped by transcranial magnetic stimulation (TMS) using the triple stimulation technique (TST) in 11 normal individuals. Stimuli were given while the subjects were (a) distracted, (b) concentrating on their target (recorded) hand, and (c) concentrating on their contralateral hand. Within seconds, the proportion of excited motor units increased, similarly in all subjects, by an average of 70% from (a) to (b), and by 48% from (a) to (c). At the optimal stimulation site, results obtained with the TST were compared to those of conventional MEPs. The TST proved superior in detecting the rapid changes of the motor output caused by the non-specific mental tasks studied.

A clinical study of motor evoked potentials using a triple stimulation technique.

Amplitudes of motor evoked potentials (MEPs) are usually much smaller than those of motor responses to maximal peripheral nerve stimulation, and show marked variation between normal subjects and from one stimulus to another. Consequently, amplitude measurements have low sensitivity to detect central motor conduction failures due to the broad range of normal values. Since these characteristics are mostly due to varying desynchronization of the descending action potentials, causing different degrees of phase cancellation, we applied the recently developed triple stimulation technique (TST) to study corticospinal conduction to 489 abductor digiti minimi muscles of 271 unselected patients referred for possible corticospinal dysfunction. The TST allows resynchronization of the MEP, and thereby a quantification of the proportion of motor units activated by the transcranial stimulus. TST results were compared with those of conventional MEPs. In 212 of 489 sides, abnormal TST responses suggested conduction failure of various degrees. By contrast, conventional MEPs detected conduction failures in only 77 of 489 sides. The TST was therefore 2.75 times more sensitive than conventional MEPs in disclosing corticospinal conduction failures. When the results of the TST and conventional MEPs were combined, 225 sides were abnormal: 145 sides showed central conduction failure, 13 sides central conduction slowing and 67 sides both conduction failure and slowing. It is concluded that the TST is a valuable addition to the study of MEPs, since it improves detection and gives quantitative information on central conduction failure, an abnormality which appears to be much more frequent than conduction slowing. This new technique will be useful in following the natural course and the benefit of treatments in disorders affecting central motor conduction.

Transcranial stimulation excites virtually all motor neurons supplying the target muscle. A demonstration and a method improving the study of motor evoked potentials.

Transcranial stimulation has become an established method in the evaluation of corticospinal tract function. Clinical studies mainly address slowing of conduction through measurement of increased central conduction time (CCT) and 'failures' of conduction through observation of marked reductions in the size of the motor evoked potential (MEP). While CCT is of great interest in detecting subclinical slowing of conduction, the method discloses only gross failures of conduction, since the size of the MEP varies markedly between normal subjects and from one stimulus to another, leading to a broad range of normal values. Furthermore, transcranial stimulation does not appear to achieve depolarization of all spinal motor neurons leading to the target muscles, since in most normal subjects MEPs are smaller in amplitude than the responses evoked by peripheral nerve stimulation. We have developed a triple stimulation technique (TST) which, through two collisions, links central to peripheral conduction and suppresses desynchronization of MEPs. This technique shows that transcranial stimulation does achieve depolarization of all, or nearly all, spinal motor neurons supplying the target muscle in healthy subjects. Our data thus demonstrate that the amplitudes of MEPs are (i) smaller than those of peripheral responses, mostly due to phase cancellation of the action potentials caused by the desynchronization occurring within the corticospinal tract or at spinal cell level and (ii) variable between normal subjects and from one stimulus to another, mostly due to variability of this desynchronization. This technique provides new insights into normal corticospinal tract conduction. It will improve detection and quantification of central motor conduction failures.

[Interhemispheric disconnection, Balint's syndrome and persistent anarthria: Marchifava-Bignami disease with white matter hemorrhage]. / Dysconnexion interhémisphérique, syndrome de Balint et troubles arthriques persistants: maladie de Marchiafava-Bignami avec hémorrhagie de la substance blanche.

A 37-year-old alcoholic right-handed man developed a complex neuropsychological picture following a mild head injury and a severe confusional state. Prominent features were Balint's syndrome, signs of interhemispheric deconnection, and speech disorders with anarthria and dysprosody. Iterative CT scans showed pathognomonic hypodensities of the genu and splenium of corpus callosum, confirmative of Machiafava-Bignami disease. After a two years follow-up, a favourable outcome was observed despite haemmoragic transformation of bilateral necrotic lesions of the parietal white matter, an exceptional neuropathological fact. This case is demonstrative of the possibility of articulate speech impairment when lesions of both corpus callosum and subcortical white matter are present. It also raises several aetiopathogenic problems which are discussed.

Seroepidemiology, viral isolation, and molecular characterization of human T cell leukemia/lymphoma virus type I from La Réunion Island, Indian Ocean.

Data indicate the presence in the Seychelles Islands of a high level of human T cell leukemia/lymphoma virus type I (HTLV-I) endemicity as well as the presence of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). We present here the results of an hospital survey performed since 1988 in La Réunion Island, located in the Indian Ocean southeast of the Seychelles archipelago, aimed at evaluating HTLV-I endemicity, detecting HTLV-I-associated diseases, and characterizing viral isolates. Seven individuals were found to have HTLV-I-specific antibodies in their sera. These include 3 of 257 patients from St. Pierre Hospital, 1 of them exhibiting a typical clinical feature of TSP/HAM (the first described case in this region), 1 blood donor of 3900, and 3 relatives. A further nine individuals exhibiting only "gag-encoded proteins" by Western blot (p19 and/or p24 bands) were found negative by polymerase chain reaction using LTR, pol, and tax HTLV-I specific primers. A long-term T cell line, designated Mel.J, exhibiting T cell activation markers (CD4+, CD25+, HLA-DR+), and producing HTLV-I antigens and viral particles, was established from one of the HTLV-I,-seropositive patients. The sequence of a 522-bp fragment corresponding to the carboxy terminus of gp46 and the majority of gp21 were determined for five HTLV-I-seropositive individuals, including the TSP/HAM patient. Alignment and phylogenetic comparison of these five nucleotide sequences with all the 53 other available HTLV-I env sequences demonstrated that the virus from La Réunion Island belongs to the group of the HTLV-I cosmopolitan subtype and is not related to the Melanesian HTLV-I variants.

[Thrombosis of the ending internal carotid artery complicating giant aneurysm]. / Thrombose de la terminaison de l'artère carotide interne compliquant un anévrysme géant.

A 30-year old man suddenly developed left hemiplegia. CT scan and cerebral angiography showed complete thrombosis of a right internal carotid giant aneurysm. Anterograde propagation of the thrombus in the parent artery led to ipsilateral hemispheric infarction, an exceptional presenting symptom of such vascular malformation. The diagnostic and etiopathogenic aspects are briefly discussed.