Reduced 123I-MIBG uptake in the parotid and submandibular glands in patients with Parkinson's disease identified using a quantitative semi-automatic method.

OBJECTIVES: To analyze 123I-metaiodobenzylguanidine (MIBG) uptake in the parotid and submandibular glands in patients with Parkinson's disease (PD) in comparison with controls, and to compare MIBG uptake between those glands and the myocardium. Furthermore, we aimed to identify the relationships between clinical features and MIBG uptake. METHODS: We recruited 77 patients with PD and 21 age-matched controls. We assessed MIBG scintigraphy in the major salivary glands and myocardium. We calculated the MIBG uptake ratio in the parotid glands/mediastinum (P/M), submandibular glands/mediastinum (S/M), and heart/mediastinum (H/M) using a quantitative semi-automatic method. We investigated the correlations between MIBG uptake and clinical features. RESULTS: The P/M and H/M ratios in the early and delayed phases were significantly reduced in PD patients compared to controls, while the delayed phase S/M ratio was reduced in PD patients compared to controls. The P/M ratio correlated with the S/M ratio, while neither the P/M nor S/M ratio correlated with the H/M ratio. Between PD patients and controls, sensitivity and specificity were 54.8% and 59.1% for the delayed phase P/M ratio, while sensitivity and specificity were 59.5% and 61.0% for the delayed phase S/M ratio, respectively. Furthermore, sensitivity and specificity for the delayed phase H/M ratio were 85.7% and 79.2, respectively. CONCLUSION: MIBG uptake in the parotid and submandibular glands was reduced in patients with PD. Furthermore, sympathetic denervation in the major salivary glands and myocardium might progress independently. Our findings suggest a new aspect of the pathological distribution of PD.

Effects of Long-term Hybrid Assistive Limb Use on Gait in Patients with Amyotrophic Lateral Sclerosis.

Objective To assess the long-term effects of hybrid assistive limb (HAL) treatment on gait in patients with amyotrophic lateral sclerosis (ALS). Methods Three courses of treatment with HAL were administered to three women with ALS. Each course had a four- to five-week duration, during which the treatment was performed nine times, with a rest period of at least two months between each course. Gait ability (2-minutes-walk and 10-m-walk tests), ALS Functional Rating Scale-Revised, and respiratory function tests were performed before and after each treatment course. Patients Patients diagnosed with ALS, according to the updated Awaji criteria, by board-certified neurologists in the Department of Neurology and Department of Rehabilitation Medicine, Toho University Omori Faculty of Medicine between January and December 2019 were recruited. Results The average time from the start to the end of the 3 courses was 319.7±33.7 days. A multiple regression analysis was performed for the 2-minutes-walk and 10-m-walk tests, using the baseline value, each participant's ID, and time point as covariates. Changes after each course were considered outcomes. Following the 3 treatment courses, the 2-minutes walk distance improved by 16.61 m (95% confidence interval, -9.33-42.54) compared with the baseline value, but this improvement was not statistically significant (p=0.21). However, cadence significantly improved by 1.30 steps (95% confidence interval, 0.17-2.42; p=0.02). Conclusion Long-term, repetitive HAL treatments may help patients with ALS maintain their gait.

Robot-assisted training using hybrid assistive limb ameliorates gait ability in patients with amyotrophic lateral sclerosis.

OBJECTIVE: The Hybrid Assistive Limb (HAL; CYBERDYNE, Inc., Japan) is a wearable robot device that provides effective gait assistance according to voluntary intention by detecting weak bioelectrical signals of neuromuscular activity on the surface of the skin. We used HAL for patients with amyotrophic lateral sclerosis (ALS) to determine whether HAL training had an effect on their gait ability. METHODS: We conducted a single-center, single-arm, observational study. Patients with ALS underwent HAL training once per day (20-40 min per session) for 9-10 days for at least 4 weeks. Gait ability was evaluated using the 2-minute walk test, the 10-meter walk test without the assistance of HAL, and activities of daily living (ADL) using the Barthel Index and Functional Independence Measures before and after a full course of HAL training. RESULTS: There were no dropouts or adverse events during the observation period. Gait function improved after HAL training. The 2-minute walk test revealed a mean gait distance of 73.87 m (36.65) at baseline and 89.9m (36.70) after HAL training (p = 0.004). The 10-meter walk test showed significantly improved cadence, although gait speed, step length on the 10-m walk, or ADL measurements did not change significantly. CONCLUSIONS: Although HAL is not a curative treatment for ALS, our data suggest that HAL may be effective in ameliorating and preserving gait ability in patients with ALS.

Dopamine Transporter Imaging in Parkinson Disease: Progressive Changes and Therapeutic Modification after Anti-parkinsonian Medications.

Parkinson disease (PD) is a slowly progressive neurodegenerative disease characterized by the loss of dopaminergic neurons and terminals in the nigrostriatal system. Dopamine transporter (DAT) imaging is widely performed for the differential diagnosis of PD and other degenerative parkinsonism from essential tremor, vascular parkinsonism, and drug-induced parkinsonism. DAT is the plasma membrane carrier specific to dopamine neurons that are responsible for re-uptaking dopamine from the synaptic cleft back into the nerve ending. DAT binding might reflect striatal presynaptic dysfunction or DAT expression in PD patients. Longitudinal studies of DAT imaging have reported progressive changes from early PD patients. This imaging may be used as a progressive biomarker. Follow-up DAT imaging for therapeutic interventions has been applied for several anti-parkinsonian drugs. We herein review the progressive changes and therapeutic modification of DAT binding by anti-PD medications in early PD patients.

Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study.

This study examined whether zonisamide (ZNS) cotreatment delays dopamine transporter (DAT) reduction on SPECT in Parkinson disease (PD) patients. The study participants met the following criteria: (i) age ≥ 40 years; (ii) HY stage = 2 or 3; (iii) average specific binding ratio (SBR) ≥2.00; (iv) levodopa administration without a prior history of ZNS use before the first DAT-SPECT (baseline). Attending physicians initially determined whether ZNS (25 mg/day) should be used or not. Levodopa and other anti-PD medications were not restricted. The second DAT-SPECT (endpoint) was conducted 1.2 ±â€¯0.2 years after the first DAT-SPECT. Clinicoradiological changes of HY stage, UPDRS parts II to IV, dyskinesia subscore, and SBR were calculated. Statistical differences were analyzed by Student's t-test, ANOVA, or multilogistic analysis. ZNS cotreatment improved wearing off and prevented the development of dyskinesia without additional administration of selegiline, entacapone, and dopamine receptor agonists. The endpoint SBR reduced significantly in the non-ZNS group compared to the baseline (P < .01). The SBR decline rate reduced significantly in the ZNS group (P < .01). ZNS was an independent preventive factor for SBR reduction. These results suggested a beneficial potential that ZNS preserves striatal presynaptic DAT expression and slows disease progression in early-stage PD.

Preventive Treatment with Lomerizine Increases Cerebral Blood Flows during the Interictal Phase of Migraine.

BACKGROUND: Changes in regional cerebral blood flow (rCBF) were reported in migraineurs. However, little is known how preventive medications of migraine can influence rCBF. Lomerizine, a calcium channel blocker, has been used for migraine prophylaxis in Japan. We examined rCBF after lomerizine treatment. SUBJECTS AND METHODS: Migraine was diagnosed according to the criteria of the International Classification of Headache Disorders, Third Edition beta. Migraine subtype was classified into migraine with aura (MA) and migraine without aura (MO). Lomerizine (10 mg/day, per oral) was administered for 3 months. Headache Impact Test-6 (HIT-6) and blood pressure (BP) were compared at baseline and end point. Brain single photon emission computed tomography using 99mTc-ethyl cysteinate dimer was performed at the interictal period. Brain SPECT data were analyzed according to revised version of 3-dimensional stereotaxic region of interest template. Clinic-radiological variables were analyzed by paired Student's t test. RESULTS: Ten migraineurs (4 men and 6 women) participated in the present study. Mean age was 54.1 (standard deviation [SD] 10.1) years. Mean duration of migraine was 25.3 (SD 9.8) years. Migraine subtype showed 4 MA and 6 MO patients. Mean score of HIT-6 was 66.3 (SD 11.7). Lomerizine treatment decreased HIT-6 scores significantly (P < .01). BP did not differ significantly after lomerizine treatment. Lomerizine treatment increased rCBF 20% approximately in the frontal, the parietal, the temporal, and the occipital region. CONCLUSIONS: The present study indicated a significant increase in interictal rCBF after lomerizine treatment in migraineurs. The upregulation of rCBF could contribute to the antimigraine mechanism of lomerizine.

Treatment with telmisartan, a long-acting angiotensin II receptor blocker, prevents migraine attacks in Japanese non-responders to lomerizine.

Lomerizine, calcium channel blocker, is the most used medication for migraine prophylaxis in Japan. The effectiveness of this drug is reported as 50-75%. Telmisartan is angiotensin II receptor blockers which plasma half-life is 24 h. We examined whether telmisartan has preventative benefits in lomerizine non-responsive migraineurs. Lomerizine non-responders received telmisartan (20 mg/day) for 3 months after the investigation period of 3 months. Blood pressure, frequency of headache days/month, headache severity, and doses of triptans and analgesics were analyzed by Wilcoxon signed rank test. Thirty-three migraineurs (25 women and 8 men) participated in this study. Seven patients had migraine with aura and 26 patients had migraine without aura. Mean age (SD) was 46.6 (10.3) years. Mean duration (SD) of migraine was 20.4 (12.5) years. Headache severity exhibited mild degree in 5 patients, moderate degree in 9 patients and severe degree in 19 patients. Mean frequency (SD) of headache days was 10.9 (8.5) days/month. Mean usage (SD) of triptans was 4.8 (5.1) tablets/month and that of analgesics was 15.2 (22.2) tablets/month. Five patients (15%) had hypertension. Telmisartan administration had benefits in 30 patients (90%). This medication significantly decreased frequency of headache days (P < 0.01) and headache severity (P < 0.01). Doses of triptans were reduced at one-third (P < 0.05) and those of analgesia at one-fifth after telmisartan treatment (P < 0.01). After telmisartan, mean (SD) of systolic blood pressure was significantly decreased (P < 0.05). The present study supported that telmisartan treatment had preventive effects in 90% of lomerizine non-responders. Telmisartan non-responders (10%) exhibited chronic migraine and long migraine duration.

Clinical Profile and Changes of Serum Lipid Levels in Epileptic Patients after Cerebral Infarction.

BACKGROUND: Antiepileptic drugs (AEDs) may increase development of dyslipidemia and cerebrovascular disease (CVD). We examined the clinical profile and changes of serum lipid levels after AED monotherapy in patients with poststroke epilepsy (PSE) after cerebral infarction (CI). SUBJECTS AND METHODS: Medical records were reviewed in consecutive 2144 CI patients. Monotherapy of valproate, carbamazepine (CBZ), phenytoin (PHT), zonisamide, levetiracetam, or lamotrigine was performed in PSE patients. Serum lipid levels were measured before and at 3 months after AED treatment. RESULTS: The prevalence of PSE was 7.0% in CI patients. The TOAST etiology disclosed large-artery atherosclerosis in 68 patients (45%), cardioembolism in 63 patients (42%), and undetermined cause in 19 patients (13%). CVD risk profile showed obesity of 18 patients (12%), current smoker of 30 patients (20%), hypertension of 75 patients (50%), diabetes mellitus of 32 patients (21%), dyslipidemia of 15 patients (10%), and atrial fibrillation of 63 patients (42%). CBZ or PHT administration increased serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels significantly compared to baseline and AED-untreated controls. Those levels were not increased significantly in other AED and control groups. Serum high-density lipoprotein-cholesterol and triglyceride levels did not differ statistically in all groups. CONCLUSIONS: The prevalence of post-CI epilepsy was 7.0%. The pathogenesis contributed to atherothrombosis and cardioembolism. CBZ or PHT administration increased serum TC and LDL-C significantly. Thus, we should pay more attention to serum lipid levels in patients receiving cytochrome P450 (CYP)-induced AEDs, and might considerer switching to non-CYP-induced AEDs in patients with unfavorable serum lipid changes.

Transdermal Patch of Rotigotine Attenuates Freezing of Gait in Patients with Parkinson's Disease: An Open-Label Comparative Study of Three Non-Ergot Dopamine Receptor Agonists.

Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients. Methods Rotigotine (maintenance doses of 9-27 mg/day) was administered in 51 patients, 36 patients received pramipexole LA (1.5-4.5 mg/day) and 35 patients received ropinirole CR (8-16 mg/day). The Unified PD Rating Scale (UPDRS) parts I-IV, FOG questionnaire (16 items) and wearing off time were examined from baseline to 7 months after DA administration. UPDRS parts I-IV were evaluated during on time and FOG was recorded during off time if patients experienced wearing off. Results A total of 111 patients completed the study. UPDRS parts II-III scores and wearing off time were significantly reduced after each DA treatment compared to baseline. FOG was found in 54 patients (49%). Most patients developed FOG during off time only. FOG scores were significantly decreased at 2 months after rotigotine treatment whereas pramipexole LA and ropinirole treatment did not alter FOG scores. Conclusion The present study indicates that transdermal patch of rotigotine attenuated the FOG off time. The similar binding affinities to dopamine receptors between rotigotine and dopamine, and 24 hours steady hemodynamics could contribute to the therapeutic mechanism of rotigotine on FOG in PD patients with wearing off.

Demyelinating hypertrophic inferior alveolar nerve mimicking a nerve tumor.

We herein report a patient with demyelinating inferior alveolar nerve hypertrophy, which was initially suspected to have a nerve tumor. A 39-year-old woman with childhood-onset polyneuropathy presented with tooth pain and visited a dental clinic. An X-ray examination of the mandible revealed enlargement of the mandibular canal, and a nerve tumor was suspected. CT scan and MRI showed hypertrophy of the inferior alveolar nerve along its entire length. We diagnosed the patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which was supported by the spontaneous recovery reported in her childhood, the results from a nerve conduction study and MRI data. CIDP should be considered in the differential diagnosis of mandibular canal enlargement.

Somatic instability of expanded CAG repeats of ATXN7 in Japanese patients with spinocerebellar ataxia type 7.

PURPOSE: Spinocerebellar ataxia type 7 (SCA7) is a disease characterized by progressive ataxia syndrome and retinal degeneration. SCA7 is caused by expansion of CAG repeats in the ataxin 7 gene. The purpose of this study was to describe the clinical and genetic features in a two-generation Japanese family with SCA7. METHODS: The female proband underwent systemic examinations that included neurological and ophthalmic examinations and magnetic resonance imaging (MRI) scans. We interviewed her affected mother about the clinical history at the bedside. Genomic DNA was purified from peripheral blood lymphocytes. The number of CAG repeats in the proband, and her affected mother was determined by a polymerase chain reaction-based assay that used the GeneScan analysis software. RESULTS: Neurological examinations showed limb ataxia, truncal ataxia, explosive speech, and hyperactive deep tendon reflexes. The MRI scans showed atrophy of the cerebellum and fundus of pons and tegmentum. Ophthalmologically, loss of visual acuity, macular degenerations, and central scotomas were observed in both eyes. Full-field electroretinography revealed reduced cone responses with preserved rod responses. The mother had hand-motion vision. Genetic analysis revealed that various expanded CAG repeat lengths (43-57) and the peak number of repeats (47 and 48) were the same in both patients. CONCLUSIONS: The proband exhibited a typical phenotype of SCA7, which includes cone dystrophy and spinocerebellar ataxia. Genetic analysis demonstrated somatic instability of the CAG repeats in the blood lymphocytes and suggested that there was no genetic anticipation through the maternal transmission.

Reciprocal Regulation of Substance P and IL-12/IL-23 and the Associated Cytokines, IFNγ/IL-17: A Perspective on the Relevance of This Interaction to Multiple Sclerosis.

UNLABELLED: The neuropeptide substance P (SP) exhibits cytokine-like properties and exerts different effects in autoimmune inflammation. Various immune cells express SP and its neurokinin-1 receptor (NK1R) isoforms. A role for SP has been demonstrated in a number of autoimmune conditions, including multiple sclerosis (MS). In this work, we studied the role of SP and NK1R in human immune cells with a focus on their relationship with IL-12/IL-23 family cytokines and the associated IFN-γ/IL-17. AIMS: (1) To determine the role of SP mediated effects on induction of various inflammatory cytokines in peripheral blood mononuclear cells (PBMC); (2) to investigate the expression of SP and its receptor in T cells and the effects of stimulation with IL-12 and IL-23. Quantitative real-time PCR, flow cytometry, ELISA, promoter studies on PBMC and primary T cells from healthy volunteers, and Jurkat cell line. Treatment with SP significantly increased the expression of IL-12/IL-23 subunit p40, IL-23 p19 and IL-12 p35 mRNA in human PBMC. Expression of NK1R and SP in T cells was upregulated by IL-23 but a trend was observed with IL-12. The IL-23 effect likely involves IL-17 production that additionally mediates IL-23 effects. Mutual interactions exist with SP enhancing the cytokines IL-23 and IL-12, and SP and NK1R expression being differentially but potentially synergistically regulated by these cytokines. These findings suggest a proinflammatory role for SP in autoimmune inflammation. We propose a model whereby immunocyte derived SP stimulates Th1 and Th17 autoreactive cells migrating to the central nervous system (CNS), enhances their crossing the blood brain barrier and perpetuates inflammation in the CNS by being released from damaged nerves and activating both resident glia and infiltrating immune cells. SP may be a therapeutic target in MS.

Donepezil-induced cervical dystonia in Alzheimer's disease: a case report and literature review of dystonia due to cholinesterase inhibitors.

We herein report an 81-year-old woman with Alzheimer's disease (AD) in who donepezil, a cholinesterase inhibitor (ChEI), caused cervical dystonia. The patient had a two-year history of progressive memory disturbance fulfilling the NINCDS-ADRDA criteria for probable AD. Mini-Mental State Examination score was 19/30. The remaining examination was normal. After a single administration of donepezil (5 mg/day) for 10 months, she complained of dropped head. Neurological examination and electrophysiological studies supported a diagnosis of cervical dystonia. Antecollis disappeared completely at 6 weeks after cessation of donepezil. Dystonic posture can occur at various timings of ChEI use. Physicians should pay more attention to rapidly progressive cervical dystonia in ChEI-treated AD patients.

A case of superficial hemisensory dysfunction due to operculo-insular infarction: radiological depiction of thalamocortical projections to the secondary somatosensory cortex.

A 64-year-old obese man developed hypesthesia in the left arm and leg. Neurological examination revealed decreased senses of pain, touch, and temperature in the left face, arm, trunk, and leg. Remaining functions were normal. Electrocardiogram showed atrial fibrillation. Somatosensory-evoked potentials using the stimulation in the median nerve were normal on both sides. Brain magnetic resonance imaging revealed acute infarction in the right parietal operculum and insula. There were no pathognomonic lesions in the postcentral gyrus, the thalamus, or the brain stem. Cardioembolic operculo-insular infarction was diagnosed. Diffusion tensor tractography map displayed the thalamocortical projections to the primary and the secondary somatosensory cortex (S2). These radiological findings supported that the operculo-insular lesion could disrupt the thalamo-S2 pathway. Thus, the thalamocortical disconnection between the thalamus to the S2 could cause superficial hemisensory dysfunction in the present patient.

A case of sinus arrest and post-hiccup cough syncope in medullary infarction.

We describe asymptomatic sinus arrest and post-hiccup cough syncope in a patient with medullary infarction. A 78-year-old woman developed arrhythmia, hiccup, and cough syncope attacks. Neurological examination was not remarkable. Cough syncope occurs after hiccup attacks. Bradycardia and decreased blood pressure were also present after the beginning cough. Holter 24-hour electrocardiography monitor exhibited 65 episodes of asymptomatic sinus arrest more than 3 seconds. Magnetic resonance imaging disclosed acute infarction in the bilateral medial regions and the right tegmentum of the upper and middle medulla oblongata. Cerebral angiography showed severe atherosclerotic changes in the vertebral arteries. These clinicoradiological findings suggested that a distinct topography of medullary lesions could cause a series of cardiovascular and respiratory dysfunction. Thus, physicians should pay more attention to the medullary lesion in patients with arrhythmia and syncope.

Ophthalmoplegia and flaccid paraplegia in a patient with anti-NMDA receptor encephalitis: a case report and literature review.

We herein report the case of a 26-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis presenting with ophthalmoplegia and flaccid paraplegia. She developed disorientation and hallucination after fever and vomiting. Hypothermia, hypoventilation, hypertension, paralytic ileus and hyponatremia were present. Neurological examination showed mild consciousness disturbance and bilateral ophthalmoplegia on admission, flaccid paraplegia with leg areflexia on Day 4. Anti-NMDAR antibodies were detected in the serum and cerebrospinal fluid samples. Motor nerve conduction velocity was decreased in the tibial and peroneal nerves. F-wave amplitudes were reduced in the tibial nerve. MRI disclosed lesions in the callosal splenium, hippocampus and cerebral subarachnoid regions. In addition to various encephalitic symptoms, physicians should pay more attention to peripheral nerve damage in patients with anti-NMDAR encephalitis.

Presence of paraneoplastic antibodies in non-carcinomatous patients with neurological involvements of unknown cause.

BACKGROUND: Paraneoplastic antibodies (PAs) play a crucial role in the diagnostic approach of paraneoplastic neurological syndrome (PNS). We clarified the frequency and the clinical profile of PA-positive non-carcinomatous patients with neurological involvements of unknown cause. METHODS: PAs were analyzed in sera of 222 consecutive non-carcinomatous patients (122 men and 100 women) defined as acute or subacute onset of unknown-causative symptoms involving the neuromuscular junction, the central and/or the peripheral nervous system between 2006 and 2009. PAs contained antineuronal nuclear autoantibody type 1, 2, 3, Purkinje cell cytoplasmic autoantibody type 1, 2, anti-Tr, amphiphysin, CRMP-5, P/Q-type, N-type voltage-gated calcium channels (VGCC), voltage-gated potassium channel complex (VGKCC) and neuronal acetylcholine receptor (nAChR) antibodies. PA-seropositive patients received detailed examination of carcinoma in the whole body for the following 2 years. RESULTS: Nine patients were PA-positive. VGKCC antibodies were found in four patients, P/Q-type VGCC antibodies in two, N-type VGCC antibodies in two and nAChR antibodies in one. Neurological features revealed limbic encephalitis in four patients, sensorimotor neuropathy in three and Lambert-Eaton myasthenic syndrome in two. One year later, 2 patients developed myelodysplastic syndrome and lung adenocarcinoma (one patient each). CONCLUSION: We conclude that PA-seropositive frequency is 4.1% in non-carcinomatous neurological patients at examination. VGKCC, P/Q-type and N-type VGCC, and nAChR antibodies have benefits for screening non-carcinomatous PNS patients with acute or subacute neurological deficits of unknown cause.

Relationship between cervical cord 1H-magnetic resonance spectroscopy and clinoco-electromyographic profile in amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons, leading to limb paralysis and respiratory failure. METHODS: C1-C3 cord (1) H-magnetic resonance spectroscopy ((1) H-MRS) was performed in 19 patients with ALS and 20 controls. N-acetylaspartate (NAA), choline-containing compounds, creatine plus phosphocreatine (Cr), and myo-Inositol (m-Ins) were measured. ALS functional rating scale-revised (ALSFRS) and forced vital capacity (FVC) were assessed. The rates of decline were calculated at 6 months before and after (1) H-MRS. RESULTS: NAA/Cr and NAA/m-Ins were decreased significantly, and m-Ins/Cr was increased significantly in ALS patients compared with controls. NAA/Cr and NAA/m-Ins were correlated with ALSFRS and FVC and inversely linked to the decline rates. NAA/Cr, NAA/m-Ins, and m-Ins/Cr were altered markedly in 9 patients with denervation and neurogenic changes in both C2 paraspinal and upper limb muscles. CONCLUSIONS: These metabolite ratios were associated with disease progression and ongoing denervation in neck and hand muscles. C1-C3 cord (1) H-MRS might reflect anterior horn cell damage causing neck/arm weakness and respiratory dysfunction in ALS patients.