Electromyographic findings in primary lateral sclerosis during disease progression

ObjectiveTo characterize electromyographic (EMG) findings in patients with primary lateral sclerosis (PLS) during the disease course.MethodsIn PLS patients we scored spontaneous activity and motor unit action potential (MUP) pattern on EMG. We compared patients according to lower (group A) and higher (group B) EMG scores. EMG studies were repeated at intervals longer than 11 months; two or three repeat studies were required for inclusion in the analysis.ResultsWe studied 22 patients. Fasciculation potentials were found in 13 and fibrillations/positive sharp waves (fibs/sw) in 3 patients. Both were stable over time. Most patients had MUP abnormalities (n = 17), with worsening in the lower limbs in patients with three evaluations (p = 0.010). Compared to group A (n = 12), patients of group B (n = 10) had a significant shorter disease duration (median 10.9 vs 15.2 years, p < 0.001), lower functional score at both first (39 vs 45, p = 0.034) and last (29 vs 38, p = 0.003) evaluations, and had a faster functional decline (0.19 vs 0.08, p = 0.004).ConclusionsMost PLS patients showed minor and stable EMG abnormalities, without progression to ALS. Patients with more EMG abnormalities have a faster progression.SignificanceEMG abnormalities in most PLS patients are minor and stable.     

Motor-evoked responses in primary lateral sclerosis.

Primary lateral sclerosis (PLS) may be distinguished on the basis of clinical and pathological features from amyotrophic lateral sclerosis (ALS). The former is featured by a much longer clinical course, exclusively upper motor neuron findings, losses of precentral pyramidal neurons, and preservation of anterior horn cells. Electrophysiological studies of 7 PLS cases have shown normal peripheral motor conduction, absent or very delayed motor-evoked potentials, the occasional late development of denervation activity in distal muscles, and normal somatosensory-evoked potentials.     

Reliability of phrenic nerve conduction study: In healthy controls and in patients with primary lateral sclerosis

ObjectivePhrenic nerve conduction study is a marker of hypoventilation in amyotrophic lateral sclerosis. We aimed to evaluate its intra-rater reliability in healthy subjects and in a cohort of Primary Lateral Sclerosis (PLS) patients.MethodsEighteen healthy subjects and 16 PLS patients were included. All subjects underwent three phrenic nerve conduction evaluations (time interval: 1 week for healthy controls; 1 year for PLS patients). We analyzed intra-rater reliability for five parameters of the diaphragmatic motor response: latency; negative-peak duration, area and amplitude; peak-to-peak amplitude.ResultsHealthy subjects showed excellent inter-test reliability for most parameters (coefficients of variation <10%). In PLS patients coefficients of variation resulted <10% for latency and peak-to-peak amplitude, <20% for remaining parameters. Inter-test reliability was excellent for latency and peak-to-peak amplitude [intra-class correlation coefficient (ICC) > 0.9] and good for negative-peak amplitude and area (ICC 0.75 ≥ 0.9); duration was not reliable (ICC = 0.383). Negative peak and peak-to-peak amplitude had the least random error (respectively ±0.136 mV and ± 0.177 mV). All parameters showed homoscedasticity (R2 < 0.1).ConclusionsIntra-rater reliability is high for phrenic nerve study, especially for latency, peak-to-peak and negative-peak amplitude.SignificancePhrenic nerve conduction study is a reliable method to monitor respiratory function.     

Frontotemporal dementia with ubiquitinated neuronal inclusions presenting with primary lateral sclerosis and parkinsonism: clinicopathological report of an autopsy case

We report a case displaying upper motor sign, parkinsonism, and behavioral abnormality, with marked degeneration of the precentral cortex, neostriatum and frontotemporal lobes, as well as ubiquitinated neuronal inclusions. The patient was a 66-year-old male at the time of death. At age 57, he noticed progressive difficulties in speaking and swallowing. At age 60, he was severely anarthric and displayed emotional lability and incontinence. Neurologically, very poor movement of tongue was observed, but without atrophy or fasciculation. Deep tendon reflexes were hyperactive. Grasp reflex and snout reflex were also positive. Needle electromyography revealed no abnormalities. A diagnosis of primary lateral sclerosis and character change was made. At age 62, he developed bradykinesia and rigidity of the neck and all extremities. Treatment with carbidopa-levodopa was initiated, but resulted in minimal improvement. At age 65, he was bed-ridden, and had repeated occurrences of aspiration pneumonia; he died of pneumonia. Neuropathological examination revealed marked atrophy of the frontal and temporal lobes with Betz cells completely absent and moderate atrophy of the neostriatum. The spinal cord and nerve roots appeared normal. Immunohistochemically, ubiquitin-positive but tau-negative intraneuronal inclusions were found in the frontal and temporal cortices, including the precentral cortex and the hippocampal dentate gyrus, and the neostriatum. This case could be included with inclusion-associated disorders such as frontotemporal dementia or amyotrophic lateral sclerosis with dementia, and furthermore, predominant upper motor sign and parkinsonism could represent phenotypes of clinical manifestations with such inclusions.     

Clinicopathological features of primary lateral sclerosis are different from amyotrophic lateral sclerosis

Primary lateral sclerosis (PLS) bears close resemblance to cases of amyotrophic lateral sclerosis (ALS) presenting with spasticity, but histopathological studies have shown significant difference between the two conditions. When the lower motor neurons in cases of ALS and PLS are compared with the equivalent cells of control subjects, morphometric studies indicate significantly decreased size and increased convexity (rounding) of the cell bodies only in ALS. In both disorders there is loss or shrinkage of the largest cortical motor neurons (Betz cells) in the primary motor cortex, though this change is not conspicuous in all cases of ALS. Morphometry reveals in both diseases a general reduction in the sizes of pyramidal cells in the precentral gyrus, indicating that smaller neurons are involved. The cortical motor neurons shrink more in PLS than in ALS. It is concluded that there is clear difference between ALS and PLS. In PLS, quantitative histopathological data show that the neuronal degeneration is confined to long descending pathways, notably the corticospinal system, with no concomitant involvement of lower motor neurons. In ALS, lower motor neuron degeneration occurs in all cases, whereas involvement of the motor cortex is variable.     

Telephone follow-up for patients with amyotrophic lateral sclerosis

The relentless evolution of amyotrophic lateral sclerosis (ALS), a severe neurodegenerative disorder of the upper and lower motoneurons, leads to an increasing level of disability. Most patients, during the course of the disease, become unable to attend the tertiary clinical care center and are thus prevented from enrolling in clinical trials or benefiting from specialized care and management. The main objective of this study was to verify whether the ALS functional rating scale (ALSFRS) could be reliably administered by telephone to patients, when unable to attend the ALS clinic, or to their caregivers. ALSFRS is a validated instrument that assesses the functional status and the disease progression in ALS. We first administered the functional rating scale directly in the clinic to 30 patients, with definite or probable ALS, and to their respective caregivers, and found a very high agreement between the two groups for the total score and the majority of the rating items. Next, we showed, in both patients and caregivers, a high degree of correlation between the total score of the ALSFRS measured by telephone and that reported in the clinic. This indicates that ALSFRS is a reliable instrument for monitoring the disease progression in homebound patients, even when the person contacted by telephone is the caregiver. We also performed a telephone clinic, based on an unstructured interview, with 16 ALS patients at an advanced stage of the disease and unable to attend the ALS clinic. On some occasions, the person interviewed was the caregiver. The symptoms most frequently reported were a worsening of muscle strength, swallowing and breathing problems, constipation, and inability to clear lung secretions. Several patients asked for assistive and adaptive equipment. All patients and caregivers found the telephone clinic very useful and considered it a good complement to the management and care programme.     

Disease spread through contiguity and axonal tracts in primary lateral sclerosis

Our goal in this report was to determine whether symptom progression in primary lateral sclerosis (PLS) was consistent with disease spread through axonal pathways or contiguous cortical regions. The date of symptom onset in each limb and cranial region was obtained from 45 PLS patient charts. Each appearance of symptoms in a new body region was classified as axonal, contiguous, possibly contiguous, or unrelated, according to whether the somatotopic representations were adjacent in the cortex. Of 152 spread events, the first spread event was equally divided between axonal (22) and contiguous (23), but the majority of subsequent spread events were classified as contiguous. Symptom progression in PLS patients is consistent with disease spread along axonal tracts and by local cortical spread. Both were equally likely for the first spread event, but local cortical spread was predominant thereafter, suggesting that late degeneration does not advance through long axonal tracts. Muscle Nerve 49 :439–441, 2014     

Detection of an Amadori product, 1-hexitol-lysine, in the anterior horn of the amyotrophic lateral sclerosis and spinobulbar muscular atrophy spinal cord: evidence for early involvement of glycation in motoneuron diseases

Glycation is a series of non-enzymatic reactions initiated by addition of reducing sugars to ɛ-amino group of lysine residues and α-amino group of the N terminus of proteins, leading to the formation of advanced glycation end products (AGE). It is thought to be involved in aging and various neurodegenerative conditions. In the present study using anti-1-hexitol-lysine (1-HL) antibody, Amadori product, an early glycation product, was detected in axonal spheroids in the anterior horn of amyotrophic lateral sclerosis and in atrophic neurons of spinobulbar muscular atrophy (SBMA, Kennedy disease with abnormally expanded triplet repeats in androgen receptor gene) but not in other regions of the central nervous system. Furthermore, Amadori product was undetectable in the tissues from age-matched controls. Thus, 1-HL formation could not reflect physiological aging. Received: 13 October 1998 / Revised: 31 March 1999     

Intrathecal baclofen for spasticity-related pain in amyotrophic lateral sclerosis: efficacy and factors associated with pain relief

Clinical signs and symptoms of spasticity include hypertonia, involuntary movements (spasms, clonus), decreased range of motion, contractures, and often spasm-related pain. When spasticity is refractory to medical management, patients may be referred for intrathecal baclofen (ITB) pump placement. We reviewed a cohort of amyotrophic lateral sclerosis (ALS) patients with intractable spasticity requiring ITB to further define the impact of ITB on pain relief in this patient population. From 2003 to 2005, eight patients (mean age 43.8 years; 5 men, 3 women) with ALS received ITB for pain associated with intractable spasticity at our institution. Mean disease duration preoperatively was 47.4 months, mean follow-up was 9.8 months, and pain was evaluated using a 0-10 scoring system. All patients experienced spasticity relief in response to a preoperative bolus test injection of ITB (25-50 microg) via lumbar puncture. Following ITB pump placement, the average reduction of pain was 54% (P = 0.0082). Six patients (75%) experienced pain score reduction, three of whom had complete pain relief. Postoperative pain reduction was predicted by the degree of pain reduction following preoperative ITB test injection. These results support ITB as a treatment modality for pain associated with spasticity in ALS.     

Primary lateral sclerosis; a debated entity

Two patients suffering from slowly progressing spastic paraparesis are presented. Both of them underwent a several years' follow-up, and extensive laboratory, radiological and neurophysiological investigations in order to rule out known specific causes for pyramidal tract involvement. After these exclusion studies, the diagnosis of primary lateral sclerosis (PLS) was derived. The present cases provide further evidence of the long-debated PLS as a disease entity.     

Sporadic amyotrophic lateral sclerosis resembling primary lateral sclerosis: Report of an autopsy case and a review of the literature

This report describes the clinicopathological findings of a case of sporadic amyotrophic lateral sclerosis (ALS) resembling primary lateral sclerosis (PLS). A Japanese man developed muscle weakness in the distal part of the right upper extremity at age 59. At age 60 he presented with bradycinesia and rigidity. A neurological examination revealed fasciculation and increased deep tendon reflexes in the extremities. He developed decubitus and vesicorectal disturbance 2 months before his death at age 61. The neuropathological examination revealed not only prom-inent degeneration of the pyramidal tracts, evident in the internal capsule, but also loss of Betz's cells in the motor cortex. There was relative preservation of the neurons in the hypoglossal nuclei and anterior horns of the cervical and lumbar cord. In the anterior horn of the first sacral cord, there were small aggregates of lipofuscin-laden macrophages in locations from which large cells had presumably been lost. Bunina bodies and ubiquitin-immunoreactive neuronal inclusions were present in the anterior horn cells of the spinal cord. On the basis of these clinicopathological findings, we concluded that this case was one of sporadic ALS with predominant involvement of the upper motor neuron system and exhibiting features of PLS.     

Progressive upper limb monoparesis: a form of primary lateral sclerosis? Two cases with metabolic brain imaging and transcranial magnetic stimulation

Two patients presenting an isolated, slowly-progressive clumsiness affecting one upper limb are described. Clinical evidence, regional cerebral blood flow and transcranial magnetic motor stimulation suggested that this condition resulted from a selective unilateral degeneration of the corticospinal tract. Such progressive hemiparesis may possibly be considered as a rare form of primary lateral sclerosis.     

原发性侧索硬化的临床和影像学特征

目的 探讨胀发性侧索硬化（PLS）的临床和影像学特征。方法 对3例PLS患者的临床和影像学资料进行分析。结果 本组PLS患者女2例、男1例,均为缓慢起病。其中例1首发症状为右上肢僵硬、无力,例2为两下肢僵硬、无力,例3表观为假性延髓麻痹,随病情的进展,均出现四肢痉挛性瘫痪,肌力Ⅲ～Ⅳ级,肌张力呈折刀样增高,四肢腱反射亢进,两侧踝阵孪及Babinski征（＋）,头颅MRI T2 WI可见两侧内囊、大脑脚、运动区皮质及腑桥丛底部有异常高信号,^1H磁共振波谱（^1HMRS）示在病灶区有乙酰天门冬氨酸盐（NAA）降低及NAA／肌酸（Cr）比值降低。结论 PLS的临床症状、体征和MRI有特征性改变,^1HMRS的改变也有助于诊断。     

Bereitschaftspotential in amyotrophic lateral sclerosis (ALS): lower amplitudes in patients with hyperreflexia (spasticity)

In a pilot study the Bereitschaftspotential (BP) was investigated in 16 patients suffering from amyotrophic lateral sclerosis (mean age 58.6, mean severity of the illness according to Norris ALS score 76.4 points). Comparing the total ALS group ( n = 16) with matched controls no significant differences in the BP amplitude parameters were found. However, a subgroup of 7 ALS patients with signs of pronounced spasticity (hyperreflexia) differed significantly at the central midline from matched controls and significantly in addition from patients with a lower degree of spasticity. Controls as well as patients with a lower degree of spasticity had significantly higher BP amplitudes at the midline (electrode positions C_z and P_z, P <0.05, H -test). The correlation coefficient between the hyperreflexia Norris score and the various BP parameters for the total ALS sample ( n = 16) revealed a significant correlation especially over the midline. Stronger signs of spasticity (hyperreflexia) are associated with lower amplitudes of the BP.     

The onset of amyotrophic lateral sclerosis

Two patients in whom both the neurological examination and electromyography (EMG) were normal prior to the onset of amyotrophic lateral sclerosis (ALS) are reported. In each patient, the onset of ALS some 18 months later was clearly defined clinically and confirmed by subsequent EMG studies. These unique observations show that ALS commences at a defined time, and that there is early generalisation with an initial phase of rapid progression.     

A unique pattern of astrocytosis in the primary motor area in amyotrophic lateral sclerosis

Summary We examined the primary motor area (PMA, Brodmann area 4) from 23 cases of adult-onset sporadic amyotrophic lateral sclerosis (ALS) with immunocytochemistry using anti-glial fibrillary acidic protein antibody. There was astrocytosis in the middle of the pyramidal cell layer in all cases except for one that did not present any upper motor neuron signs clinically. The astrocytosis was characterized by multiple clusters of astrocytes, some of which showed a close association with macrophages. In about a half of the cases, these multiple clusters of astrocytes became confluent and presented as a laminar astrocytosis in the middle of the pyramidal cell layer. Our studies demonstrate a unique pattern of astrocytosis in the PMA in ALS. This pattern of astrocytosis may be useful not only for diagnostic purposes, but also for a better understanding of the pathological process involving the PMA in ALS.The authors wish to dedicate this work to the late Professor Masanori Tomonaga, a former member of the editorial board of this journal and a distinguished teacher and leader in the field of neuropathologySupported in part by grants-in-aid from the Ministry of Health and Welfare of Japan and United States Public Health Service grants, NS24453, HD03110, and ES01704. A part of this study was presented at the 66th Annual Meeting of the American Association of Neuropathologists (San Francisco, 1990) with an abstract in J Neuropath Exp Neurol (1990) 49:280