OBJECTIVETo study the clinical presentations of Kennedy disease (KD) and compare the neurophysiological features between KD and amyotrophic lateral sclerosis(ALS).

METHODSNine patients with KD, 13 patients with ALS and 26 normal control subjects were recruited. The clinical presentations of KD were analyzed, and the results of nerve conduction studies and electromyography were compared among the 3 groups.

RESULTSThe rates of tongue atrophy and facial fasciculation were 100% and 88.9%, respectively, in the early course and mid-course of KD, sensory damages might be perceived. 2)The sural nerve sensory nerve action potential (SNAP) was not elicited in 56.3% of the patients with KD, and sural nerve SNAP amplitudes were significantly lower in KD (7.9. ± 3.4 µV) than in ALS patients (20.0 ± 5.2 µV) and normal control subjects (26.1 ± 16.8 µV) (P<0.05).

CONCLUSIONB The onset of clinical presentations mimicking motor neuron disease, appearance of tongue atrophy and facial fasciculation in the early and mid-course, and presence of sensory impairment with a decreased sural nerve SNAP amplitude may suggest the diagnosis of KD and should prompt a genetic test for KD.

Amyotrophic Lateral Sclerosis ; physiopathology ; Bulbo-Spinal Atrophy, X-Linked ; physiopathology ; Electromyography ; Evoked Potentials ; Humans

BACKGROUNDSingle-fiber electromyography (SFEMG) has been suggested as a quantitative method for supporting chronic partial denervation in amyotrophic lateral sclerosis (ALS) by the revised EI Escorial criteria. Although concentric needle (CN) electrodes have been used to assess jitter in myasthenia gravis patients and healthy controls, there are few reports using CN electrodes to assess motor unit instability and denervation in neurogenic diseases. The aim of this study was to determine whether quantitative changes in jitter and spike number using CN electrodes could be used for ALS studies.

METHODSTwenty-seven healthy controls and 23 ALS patients were studied using both CN and single-fiber needle (SFN) electrodes on the extensor digitorum communis muscle with an SFEMG program. The SFN-jitter and SFN-fiber density data were measured using SFN electrodes. The CN-jitter and spike number were measured using CN electrodes.

RESULTSThe mean CN-jitter was significantly increased in ALS patients (47.3 ± 17.0 μs) than in healthy controls (27.4 ± 3.3 μs) (P < 0.001). Besides, the mean spike number was significantly increased in ALS patients (2.5 ± 0.5) than in healthy controls (1.7 ± 0.3) (P < 0.001). The sensitivity and specificity in the diagnosis of ALS were 82.6% and 92.6% for CN-jitter (cut-off value: 32 μs), and 91.3% and 96.3% for the spike number (cut-off value: 2.0), respectively. There was no significant difference between the SFN-jitter and CN-jitter in ALS patients; meanwhile, there was no significant difference between the SFN-jitter and CN-jitter in healthy controls.

CONCLUSIONCN-jitter and spike number could be used to quantitatively evaluate changes due to denervation-reinnervation in ALS.

Amyotrophic Lateral Sclerosis ; physiopathology ; Electrodes ; Electromyography ; Humans ; Middle Aged ; Needles ; ROC Curve

Amyotrophic Lateral Sclerosis ; pathology ; physiopathology ; Female ; Frontotemporal Dementia ; pathology ; physiopathology ; Humans ; Male ; Middle Aged ; Psychotic Disorders ; pathology ; physiopathology

BACKGROUNDThe spectrum of abnormal behaviors in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) has been described, but its practical meaning, namely its impact on caregiver burden, has not been clearly documented in Chinese population. This study aimed to assess the distribution of abnormal behaviors in Chinese population, and to analyze the relationship between behavior changes and caregiver burden.

METHODSSixty-five patients with ALS/MND have been consecutively enrolled into registry platform of Peking Union Medical College Hospital. An investigation was performed to these patients and their caregivers using the revised ALS function rating scale, Frontal Behavioral Inventory-ALS version, the Frontal Assessment Battery, and the Caregiver Burden Inventory.

RESULTSTwenty-eight (43.1%) patients displayed abnormal behaviors of varying degrees, with one fulfilling the diagnostic criteria of frontotemporal lobe degeneration. Irritability, logopenia, and inflexibility ranked top 3 of abnormal behavior list. Correlation analysis revealed that the degree of behavioral change and frontal cognitive status were significantly associated with caregiver burden, with more extensive impact from disinhibitive behaviors. Analysis of covariance analysis showed that after associated factors were corrected, caregivers of patients with moderate to severe behavior change reported significantly heavier developmental burden, physical burden, and total burden than those with no behavioral change.

CONCLUSIONSNeurobehavioral symptoms could present in around 40% of Chinese patients with ALS/MND, and the distribution of these behaviors was also unique. Besides, abnormal behaviors were highly related to caregivers' burden.

Adult ; Aged ; Amyotrophic Lateral Sclerosis ; physiopathology ; psychology ; Behavioral Symptoms ; physiopathology ; psychology ; Caregivers ; psychology ; Female ; Humans ; Male ; Middle Aged ; Quality of Life

BACKGROUNDSingle fiber electromyography (SFEMG) is a sensitive technique for detecting abnormalities in neuromuscular transmission and is mainly used in the diagnosis of neuromuscular junction disorders, such as myasthenia gravis. While the process of denervation-reinnervation in amyotrophic lateral sclerosis (ALS) can also result in immature collateral nerve terminals and instability of neuromuscular transmission, the purpose of this study was to investigate the changes and clinical values of SFEMG in patients with ALS.

METHODSVolitional SFEMG was performed on the extensor digitorum communis (EDC) of 78 patients with ALS (men 52, women 26) who had been previously diagnosed by history, clinical features, and neurophysiological studies. The mean jitter, the percentage of jitter >55 micros, the impulse blocking percentage, and fiber density (FD) were determined. These results were compared to normal controls. In addition, the SFEMG indices were analyzed for correlations with the duration of ALS, the EDC strength score on the Medical Research Council (MRC) scale, and spontaneous activity detected by EMG studies.

RESULTSSFEMG indices were abnormal in all patients with ALS. Mean jitter ranged from 30 to 178 micros (mean 80.2 micros); the percentage of jitter >55 micros ranged from 5% to 100% (mean 60.5%). In addition, the impulse blocking percentage ranged from 0% to 90% (mean 28.1%) and FD ranged from 1.4 to 4.1 (mean 2.6). Mean jitter, the percentage of jitter >55 micros, and the blocking percentage in 57 patients with definite or probable ALS were significantly higher than in patients with possible or suspected ALS. MRC scores of the EDC negatively correlated with mean jitter, the percentage of jitter >55 micros, blocking percentage, and FD.

CONCLUSIONSSFEMG is the most sensitive tool for diagnosing definite or probable ALS. Increased jitter, blocking percentage, and FD can indicate the degree of immature collateral sprouts and motor end plates resulting from the progressive denervation and reinnervation associated with ALS, and may be helpful in evaluating prognosis.

Adolescent ; Adult ; Aged ; Amyotrophic Lateral Sclerosis ; physiopathology ; Electromyography ; Female ; Humans ; Male ; Middle Aged ; Muscle Fibers, Skeletal ; physiology ; Neural Conduction

BACKGROUNDIn amyotrophic lateral sclerosis (ALS), repeater F waves are increased. Accurate assessment of repeater F waves requires an adequate sample size.

METHODSWe studied the F waves of left ulnar nerves in ALS patients. Based on the presence or absence of pyramidal signs in the left upper limb, the ALS patients were divided into two groups: One group with pyramidal signs designated as P group and the other without pyramidal signs designated as NP group. The Index repeating neurons (RN) and Index repeater F waves (Freps) were compared among the P, NP and control groups following 20 and 100 stimuli respectively. For each group, the Index RN and Index Freps obtained from 20 and 100 stimuli were compared.

RESULTSIn the P group, the Index RN (P = 0.004) and Index Freps (P = 0.001) obtained from 100 stimuli were significantly higher than from 20 stimuli. For F waves obtained from 20 stimuli, no significant differences were identified between the P and NP groups for Index RN (P = 0.052) and Index Freps (P = 0.079); The Index RN (P < 0.001) and Index Freps (P < 0.001) of the P group were significantly higher than the control group; The Index RN (P = 0.002) of the NP group was significantly higher than the control group. For F waves obtained from 100 stimuli, the Index RN (P < 0.001) and Index Freps (P < 0.001) of the P group were significantly higher than the NP group; The Index RN (P < 0.001) and Index Freps (P < 0.001) of the P and NP groups were significantly higher than the control group.

CONCLUSIONSIncreased repeater F waves reflect increased excitability of motor neuron pool and indicate upper motor neuron dysfunction in ALS. For an accurate evaluation of repeater F waves in ALS patients especially those with moderate to severe muscle atrophy, 100 stimuli would be required.

Adult ; Amyotrophic Lateral Sclerosis ; pathology ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Motor Neurons ; physiology ; Neural Conduction ; physiology ; Sample Size

Activation of interferon (IFN) signaling in the central nervous system (CNS) is usually associated with inflammation. However, a robust activation of type I IFN-stimulated genes (ISGs) at pre-symptomatic stages occurs in the spinal cord of SOD1(G93A) mice, an amyotrophic lateral sclerosis (ALS) animal model, without obvious signs of inflammation. To determine if the same signaling pathway is elevated in other types of neuronal injuries, we examined the protein expression levels of an IFN-stimulated gene, ISG15, in mouse models of acute and chronic neuronal injuries. We found that ISG15 protein was dramatically increased in the brains of mice subjected to global ischemia and traumatic brain injury, and in transgenic mice overexpressing HIV gp120 protein. These results suggest that activation of ISGs is a shared feature of neuronal injuries and that ISG15 may be a suitable biomarker for detecting neuronal injuries in the CNS.
Amyotrophic Lateral Sclerosis ; physiopathology ; Animals ; Brain Injuries ; physiopathology ; Brain Ischemia ; physiopathology ; Central Nervous System ; physiopathology ; Cytokines ; metabolism ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Ubiquitins ; metabolism

BACKGROUNDDysfunctional spinal circuit may play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). The purpose of this study was to use F waves for assessment of segmental motoneuronal excitability following upper motor neuron (UMN) dysfunctions in ALS.

METHODSWe studied the F waves of 152 ulnar nerves recorded from abductor digiti minimi in 82 patients with ALS. Two groups of hands were defined based on the presence or absence of pyramidal signs in the same upper limb. The group with pyramidal signs in the upper limbs was designated as the P group, and the group without pyramidal signs in the upper limbs was designated as the NP group.

RESULTSThe mean (P < 0.001), median (P < 0.001) and maximum (P = 0.035) F wave amplitudes, mean (P < 0.001), median (P < 0.001) and maximum (P = 0.003) F/M amplitude ratio, index repeating neuron (P < 0.001) and index repeater F waves (P < 0.001) of the P group were significantly increased compared with the NP group. No significant differences were identified for F wave chronodispersion (P = 0.628), mean F wave latency (P = 0.151), minimum F wave latency (P = 0.211), maximum F wave latency (P = 0.199), F wave persistence (P = 0.738), F wave duration (P = 0.152), F wave conduction velocity (P = 0.813) and number of giant F waves (P = 0.072) between the two groups.

CONCLUSIONSIn this study, increased F wave amplitude, F/M amplitude ratio and number of repeater F waves reflected enhanced segmental motoneuronal excitability following UMN dysfunctions in ALS.

Adult ; Aged ; Amyotrophic Lateral Sclerosis ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Motor Neuron Disease ; physiopathology ; Motor Neurons ; physiology ; Neural Conduction ; physiology ; Ulnar Nerve ; physiology

OBJECTIVETo study the activation changes of the brain in patients with amyotrophic lateral sclerosis (ALS) while executing sequential finger tapping movement using the method of blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI).

METHODSFifteen patients with definite or probable ALS and fifteen age and gender matched normal controls were enrolled. MRI was performed on a 3. 0 Tesla scanner with standard headcoil. The functional images were acquired using a gradient echo single shot echo planar imaging (EPI) sequence. All patients and normal subjects executed sequential finger tapping movement at the frequency of 1-2 Hz during a block-design motor task. Structural MRI was acquired using a three-dimensional fast spoiled gradient echo (3D-FSPGR) sequence. The fMRI data were analyzed by statistical parametric mapping (SPM).

RESULTSBilateral primary sensorimotor cortex (PSM), bilateral premotor area (PA), bilateral supplementary motor area (SMA), bilateral parietal region (PAR), contralateral inferior lateral premotor area (ILPA), and ipsilateral cerebellum showed activation in both ALS patients and normal controls when executing the same motor task. The activation areas in bilateral PSM, bilateral PA, bilateral SMA, and ipsilateral cerebellum were significantly larger in ALS patients than those in normal controls (P < 0.05). Extra activation areas including ipsilateral ILPA, bilateral posterior limb of internal capsule, and contralateral cerebellum were only detected in ALS patients.

CONCLUSIONSSimilar activation areas are activated in ALS patients and normal subjects while executing the same motor task. The increased activation areas in ALS patients may represent neural reorganization, while the extra activation areas in ALS patients may indicate functional compensation.

Adult ; Amyotrophic Lateral Sclerosis ; diagnosis ; physiopathology ; Brain ; pathology ; Brain Mapping ; Female ; Fingers ; physiopathology ; Humans ; Magnetic Resonance Imaging ; instrumentation ; methods ; Male ; Middle Aged ; Movement ; physiology ; Neuronal Plasticity ; Oxygen ; blood

Background: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS. Methods: From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry; cerebral blood flow (CBF) evaluated by arterial spin labeling; functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI; and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test. Results: In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures. Conclusion Multimodal MRI could be used to monitor short-term brain changes in ALS patients.
Adult ; Amyotrophic Lateral Sclerosis ; diagnostic imaging ; physiopathology ; Brain ; diagnostic imaging ; Cerebrovascular Circulation ; Disease Progression ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Multimodal Imaging ; methods ; Prospective Studies