Yukinobu Saito

Double cortical stimulation in amyotrophic lateral sclerosis.

OBJECTIVE: Transcranial double magnetic stimulation on the motor cortex was used to investigate central motor tract function in 16 patients with amyotrophic lateral sclerosis, five with spinal muscular atrophy, and 16 age matched normal controls. METHODS: Surface EMG responses were recorded from the relaxed abductor pollicis brevis (APB) muscle. RESULTS: Responses to test stimuli were markedly attenuated by a subthreshold conditioning stimulus given at a condition-test (C-T) interval of 1-4 ms in normal controls and patients with spinal muscular atrophy, but attenuation was mild in patients with amyotrophic lateral sclerosis. In the normal controls this suppression was caused by activation of the intracortical inhibitory mechanism because responses to electrical test stimuli and the H wave were not suppressed by the same magnetic subthreshold conditioning stimulus. In amyotrophic lateral sclerosis the effect of the conditioning cortical stimulus on the H wave was also in the normal range. CONCLUSION: The intracortical inhibitory mechanism may be impaired in patients with amyotrophic lateral sclerosis.

Electrophysiological evaluation of conduction in the most proximal motor root segment

Root conduction time (RCT), defined as the time difference between M‐wave latency by cervical magnetic stimulation (CMS) and the total peripheral motor conduction time calculated from the shortest F‐wave latency, was investigated in patients with inflammatory demyelinating neuropathies (IDP) and amyotrophic lateral sclerosis (ALS). The minimal threshold for CMS also was studied. In the IDP patients, conduction in the proximal motor root segment was considered abnormal in 52% by the RCT and in 47% by the minimal threshold for CMS, whereas both were normal in 85% of the ALS patients. These findings suggest that the RCT and minimal threshold for CMS might be additional parameters for evaluating motor nerve conduction in IDP.

Conduction slowing without conduction block of compound muscle and nerve action potentials due to sodium channel block

We studied the effect of lidocaine on nerve conduction in vivo. Recovery of the compound muscle action potential (CMAP), sensory nerve action potential (SNAP), and single motor unit potential (MUP) of median nerve stimulation was recorded in four healthy volunteers after intravenous infusion of 20 ml of 0.5% lidocaine. During loading, CMAP and SNAP amplitudes rapidly decreased and their latencies increased. After recovery of the CMAP and SNAP amplitudes, nerve conduction velocity improved gradually over a period of 3-6 h, the amplitudes and configurations of CMAP and SNAP remaining unchanged. The conduction velocity of the single MUP markedly slowed before it is blocked. This indicates that maximum conduction velocity of CMAP and SNAP could be slowed by the partial inactivation of sodium channels without accompanying conduction block. Prolongation of the rise time of depolarization of the axonal membrane potential may be the active mechanism in this slowing because of sodium channel inactivation. Abnormalities in sodium channels at the nodes of Ranvier should be considered as a mechanism of conduction slowing even when there is no conduction block.

Increased corticomotoneuronal excitability after peripheral nerve stimulation in dopa-nonresponsive hemiparkinsonism

Corticomotoneuronal excitability was examined in 7 patients with dopa-nonresponsive progressive hemiparkinsonism (DNRHP) and 10 with dopa-responsive hemiparkinsonism (Parkinsons disease: PD), as well as in 10 normal subjects, by measuring change in motor evoked potentials (MEPs) using transcranial magnetic stimulation of the motor cortex after peripheral nerve stimulation. Corticobasal degeneration (CBD) was suspected clinically for the progressive dopa-nonresponsive hemiparkinsonism. Conditioning stimulation of the median nerve on the rigid side greatly increased MEP size (500-1300%) in 4 DNRHP patients as compared to the increase for the normal subjects (140-380%) at conditioning test (C-T) intervals of 40-80 ms, but stimulation on the contralateral side did not. There was no abnormal MEP facilitation on the rigid side in 10 PD patients. None of the patients with CBD had an increase in somatosensory evoked potential (SEP) size, and no patient showed hyperexcitability in SEP-recovery during C-T intervals at which there was abnormal MEP facilitation. These results indicate that there is an exaggerated effect of afferent input on corticomotoneuronal excitability in some patients with DNRHP.

Suppression of motor cortical excitability by magnetic stimulation of the cerebellum

EMG responses of the relaxed right thenar muscle evoked by magnetic stimulation over the sensorimotor cortex were suppressed by magnetic conditioning stimulation over the occiput. The optimal interstimulus interval for reduction of the EMG amplitude was 4-6 ms. The optimal conditioning position and induced current direction were 3-4 cm below the inion when the induced current in the center of the figure-8 coil flowed from right to left horizontally. It differed from that for activating the descending motor pathway. We consider this suppression to be due to the inhibition of motor cortex excitability caused by stimulation of the dentato-thalamo-cortical pathway at the dentate nuclei or superior cerebellar peduncle.

Proximal motor conduction evaluated by transcranial magnetic stimulation in acquired inflammatory demyelinating neuropathies

OBJECTIVES To evaluate conduction abnormalities in the proximal motor nerve in patients with acquired inflammatory demyelinating neuropathies by transcranial magnetic stimulation (TMS). METHODS TMS intensity and background voluntary contraction (BVC) to evoke maximal size of motor evoked potential (MEP) in hand muscle were investigated in 24 normal subjects. Effect of experimentally induced conduction block by injecting local anesthetics in the peripheral nerve on MEP size was also studied in two normal subjects. In 22 patients with inflammatory demyelinating neuropathies, maximal MEPs were recorded in the deteriorating and recovery stages of the illness. RESULTS In normal subjects, the MEP became maximal with 30-50% of maximal BVC and at more than 80% the maximal stimulator output of the 2.0 T circular coil. The change in MEP size well reflected the degree of conduction block induced by local anesthetics. Findings for patients suggested conduction abnormalities proximal to axilla in 9 patients, and that the abnormal reduction of Erb CMAP was the result of submaximal stimulation, not true conduction block, in 3 patients. The increase in MEP/wrist CMAP ratio was better correlated with improvement in muscle strength than with change in the axilla or Erb CMAP/wrist CMAP ratio. CONCLUSIONS Problems such as conduction abnormalities in the motor tract of the central nervous system could not fully be excluded, but we consider that maximal MEP size can be used to predict proximal motor nerve conduction abnormalities.

The F wave disappears due to impaired excitability of motor neurons or proximal axons in inflammatory demyelinating neuropathies.

OBJECTIVES--Investigation of pathophysiology of F wave disappearance in demyelinating neuropathies. METHODS--The peripheral motor nerve conduction was studied by motor evoked potential (MEP) on transcranial magnetic stimulation as well as conventional nerve conduction studies before and after the treatment in 26 patients with inflammatory demyelinating neuropathies. In addition, serum antiganglioside antibodies in the acute or active stage were examined. RESULTS--The F wave was abolished in 10 patients. Seven of the 10 patients showed motor evoked potentials (MEPs) on transcranial magnetic stimulation that ranged from 1-4 mV. In six of them the F wave reappeared in the recovery stage, but the MEP size did not change. This may be caused by humoral factors, because the F wave reappeared immediately after plasma exchange or intravenous immunoglobulin treatment. A correlation of F wave disappearance with the presence of serum antiganglioside antibodies was found. CONCLUSIONS--The major pathophysiology of F wave disappearance in demyelinating neuropathies is impairment of motor neuron excitability or prolonged refractoriness of the most proximal axon for backfiring. The conventional interpretation that absent F waves suggest a conduction block at the proximal site is often inadequate.

Coexistence of amyotrophic lateral sclerosis and argyrophilic grain disease: A non‐demented autopsy case showing circumscribed temporal atrophy and involvement of the amygdala

We report a case of a 68‐year‐old right‐handed man with sporadic amyotrophic lateral sclerosis (ALS) and argyrophilic grain disease (AGD) having a 22‐month duration. His initial symptoms were dysarthria and swallowing difficulty at the age of 67. Subsequently bulbar palsy and pyramidal signs developed. His cognitive functions including face recognition, personality, and behavior were not changed compared with that of before the disease onset. However, magnetic resonance imaging disclosed severe right side‐predominant temporal atrophy. The neurological diagnosis was bulbar type ALS. Pathological examination disclosed histological evidence of ALS, including loss of Betz cells and lower motor neurons, corticospinal tract degeneration, and Bunina bodies. In addition, severe neuronal loss in the bilateral temporal cortex with an anterior gradient was found. Ubiquitin‐positive inclusions were encountered in the spinal anterior horn cells and hippocampal dentate gyrus, while few ubiquitin‐positive inclusions were noted in the affected temporal cortex. The amygdala, especially the basolateral nuclear group, was severely affected by neuronal loss with tissue rarefaction. Moderate neuronal loss was encountered in the parahippocampal gyrus, and to a lesser degree, in the ambient gyrus. Unexpectedly, many argyrophilic grains, coiled bodies, tau‐positive bush‐like astrocytes, pretangles, and ballooned neurons were found in the limbic system and temporal cortex. In the hippocampus, selective tau accumulation with minor neurofibrillary changes was observed in CA2 neurons. The present case suggests that (i) ALS and AGD do rarely coexist, and (ii) when ALS patients have severe temporal atrophy, not only ALS with dementia but also concurrent AGD should be considered in the differential diagnosis.

Frontotemporal lobar degeneration with motor neuron disease showing severe and circumscribed atrophy of anterior temporal lobes.

Frontotemporal lobar degeneration (FTLD) is characterized by a variety of behavioral and psychiatric symptoms based on the dysfunction of frontal and/or temporal lobes. A 63-year-old Japanese man without a family history of neurological diseases developed progressive symptoms of frontotemporal dementia, followed by motor neuron disease (MND). Brain magnetic resonance images demonstrated severe atrophy in the anterior temporal lobes from early clinical stage. The symptoms got rapidly worsened and the patient died of respiratory failure 1year 8months after the disease onset. A postmortem study revealed severe and circumscribed atrophy in the anterior temporal lobes, and histological examination disclosed marked neuronal loss with many neuronal cytoplasmic inclusions which were immunoreactive for ubiquitin antibodies and phosphorylated TAR DNA-binding protein of 43kDa (TDP-43) antibodies in hippocampal dentate granule cells and amygdalae, as well as a few neuronal cytoplasmic inclusions without dystrophic neurites in the temporal neocortex. This case report showed typical features of FTLD-MND in clinical course and TDP-43 pathology with unusual severity and distribution of cerebral atrophy, suggesting a unique manifestation of FTLD-MND.

Successful treatment of atypical mycobacterial meningitis by fluoroquinolone

We report a case of restricted meningeal infection by atypical mycobacteria, identified by the polymerase chain reaction, in a non-immunocompromised adult successfully treated by multiple antibiotics including fluoroquinolone. New quinolones should be considered as a therapeutic option for such mycobacterial meningitis.