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Brain : a Journal of Neurology Jun 2022CANVAS caused by RFC1 biallelic expansions is a major cause of inherited sensory neuronopathy. Detection of RFC1 expansion is challenging and CANVAS can be associated...
CANVAS caused by RFC1 biallelic expansions is a major cause of inherited sensory neuronopathy. Detection of RFC1 expansion is challenging and CANVAS can be associated with atypical features. We clinically and genetically characterized 50 patients, selected based on the presence of sensory neuronopathy confirmed by EMG. We screened RFC1 expansion by PCR, repeat-primed PCR, and Southern blotting of long-range PCR products, a newly developed method. Neuropathological characterization was performed on the brain and spinal cord of one patient. Most patients (88%) carried a biallelic (AAGGG)n expansion in RFC1. In addition to the core CANVAS phenotype (sensory neuronopathy, cerebellar syndrome and vestibular impairment), we observed chronic cough (97%), oculomotor signs (85%), motor neuron involvement (55%), dysautonomia (50%), and parkinsonism (10%). Motor neuron involvement was found for 24 of 38 patients (63.1%). First motor neuron signs, such as brisk reflexes, extensor plantar responses, and/or spasticity, were present in 29% of patients, second motor neuron signs, such as fasciculations, wasting, weakness, or a neurogenic pattern on EMG in 18%, and both in 16%. Mixed motor and sensory neuronopathy was observed in 19% of patients. Among six non-RFC1 patients, one carried a heterozygous AAGGG expansion and a pathogenic variant in GRM1. Neuropathological examination of one RFC1 patient with an enriched phenotype, including parkinsonism, dysautonomia, and cognitive decline, showed posterior column and lumbar posterior root atrophy. Degeneration of the vestibulospinal and spinocerebellar tracts was mild. We observed marked astrocytic gliosis and axonal swelling of the synapse between first and second motor neurons in the anterior horn at the lumbar level. The cerebellum showed mild depletion of Purkinje cells, with empty baskets, torpedoes, and astrogliosis characterized by a disorganization of the Bergmann's radial glia. We found neuronal loss in the vagal nucleus. The pars compacta of the substantia nigra was depleted, with widespread Lewy bodies in the locus coeruleus, substantia nigra, hippocampus, entorhinal cortex, and amygdala. We propose new guidelines for the screening of RFC1 expansion, considering different expansion motifs. Here, we developed a new method to more easily detect pathogenic RFC1 expansions. We report frequent motor neuron involvement and different neuronopathy subtypes. Parkinsonism was more prevalent in this cohort than in the general population, 10% versus the expected 1% (P < 0.001). We describe, for the first time, the spinal cord pathology in CANVAS, showing the alteration of posterior columns and roots, astrocytic gliosis and axonal swelling, suggesting motor neuron synaptic dysfunction.
Topics: Cerebellar Ataxia; Gliosis; Humans; Motor Neurons; Primary Dysautonomias; Reflex, Abnormal
PubMed: 34927205
DOI: 10.1093/brain/awab449 -
NPJ Primary Care Respiratory Medicine Mar 2016
Topics: Chronic Disease; Cough; Disease Management; Humans; Reflex, Abnormal; Syndrome
PubMed: 26937873
DOI: 10.1038/npjpcrm.2016.12 -
Progress in Brain Research 2011We established that hyperreflexia is delayed after spinal transection in the adult rat and that passive exercise could normalize low frequency-dependent depression of... (Review)
Review
We established that hyperreflexia is delayed after spinal transection in the adult rat and that passive exercise could normalize low frequency-dependent depression of the H-reflex. We were also able to show that such passive exercise will normalize hyperreflexia in patients with spinal cord injury (SCI). Recent results demonstrate that spinal transection results in changes in the neuronal gap junction protein connexin 36 below the level of the lesion. Moreover, a drug known to increase electrical coupling was found to normalize hyperreflexia in the absence of passive exercise, suggesting that changes in electrical coupling may be involved in hyperreflexia. We also present results showing that a measure of spasticity, the stretch reflex, is rendered abnormal by transection and normalized by the same drug. These data suggest that electrical coupling may be dysregulated in SCI, leading to some of the symptoms observed. A novel therapy for hyperreflexia and spasticity may require modulation of electrical coupling.
Topics: Animals; H-Reflex; Humans; Movement; Muscle Spasticity; Periodicity; Reflex, Abnormal; Reflex, Stretch; Spinal Cord Injuries
PubMed: 21333809
DOI: 10.1016/B978-0-444-53825-3.00016-4 -
Indian Pediatrics Mar 2004
Topics: Child, Preschool; Corneal Opacity; Female; Humans; Pupil Disorders; Reflex, Abnormal; Reflex, Pupillary; Retinal Neoplasms; Retinoblastoma
PubMed: 15064521
DOI: No ID Found -
British Medical Journal Feb 1972
Topics: Cataract; Cerebellar Ataxia; Cholesterol; Female; Humans; Intellectual Disability; Middle Aged; Reflex, Abnormal; Tendons; Xanthomatosis
PubMed: 5008664
DOI: 10.1136/bmj.1.5796.353 -
Restorative Neurology and Neuroscience 2010To review the extent and mechanism of the recovery of vestibular function after sudden, isolated, spontaneous, unilateral loss of most or all peripheral vestibular... (Review)
Review
PURPOSE
To review the extent and mechanism of the recovery of vestibular function after sudden, isolated, spontaneous, unilateral loss of most or all peripheral vestibular function - usually called acute vestibular neuritis.
METHODS
Critical review of published literature and personal experience.
RESULTS
The symptoms and signs of acute vestibular neuritis are vertigo, vomiting, nystagmus with ipsiversive slow-phases, ipsiversive lateropulsion and ocular tilt reaction (the static symptoms) and impairment of vestibulo-ocular reflexes from the ipsilesional semicircular canals on impulsive testing (the dynamic symptoms). Peripheral vestibular function might not improve and while static symptoms invariably resolve, albeit often not totally, dynamic symptoms only improve slightly if at all.
CONCLUSIONS
The persistent loss of balance that some patients experience after acute vestibular neuritis can be due to inadequate central compensation or to incomplete peripheral recovery and vestibular rehabilitation has a role in the treatment of both.
Topics: Adaptation, Physiological; Animals; Gait Disorders, Neurologic; Humans; Nystagmus, Pathologic; Recovery of Function; Reflex, Abnormal; Reflex, Vestibulo-Ocular; Semicircular Canals; Vertigo; Vestibular Neuronitis; Vomiting
PubMed: 20086281
DOI: 10.3233/RNN-2010-0533 -
Experimental Neurology May 2012Whether dramatic or modest, recovery of neurological function after spinal cord injury (SCI) is greatly due to neuroplasticity--the process by which the nervous system... (Review)
Review
Whether dramatic or modest, recovery of neurological function after spinal cord injury (SCI) is greatly due to neuroplasticity--the process by which the nervous system responds to injury by establishing new synaptic connections or by altering the strength of existing synapses. However, the same neuroplasticity that allows locomotor function to recover also produces negative consequences such as pain and dysfunction of organs controlled by the autonomic nervous system. In this review we focus specifically on structural neuroplasticity (the growth of new synaptic connections) after SCI and on the consequent development of pain and autonomic dysreflexia, a condition of episodic hypertension. Neuroplasticity after SCI is stimulated by the deafferentation of spinal neurons below the lesion and by the expression of growth-promoting neurotrophins such as nerve growth factor (NGF). A broad range of therapeutic strategies that affect neuroplasticity is being developed for the treatment of SCI. At one end of the spectrum are therapeutic strategies that directly or indirectly increase NGF in the injured spinal cord, and have the most robust effects on neuroplasticity. At the other end of the spectrum are neuroprotective strategies focused on supporting and rescuing uninjured, or partially injured, axons; these might limit the deafferentation stimulus for neuroplasticity. In the middle of this spectrum are strategies that block axon growth inhibitors without necessarily providing a growth stimulus. The literature supports the view that the negative consequences of neuroplasticity develop more commonly with therapies that directly stimulate nerve growth than they develop in the untreated injured cord. Compared to these conditions, neuroplasticity with negative outcomes is less prevalent after treatments that that neutralize axon growth inhibitors, and least apparent after strategies that promote neuroprotection.
Topics: Animals; Autonomic Dysreflexia; Axons; Neuronal Plasticity; Pain; Reflex, Abnormal; Spinal Cord Injuries
PubMed: 22116043
DOI: 10.1016/j.expneurol.2011.11.004 -
Epilepsia Dec 2012Startle syndromes are paroxysmal and show stimulus sensitivity, placing them in the differential diagnosis of epileptic seizures. Startle syndromes form a heterogeneous... (Review)
Review
Startle syndromes are paroxysmal and show stimulus sensitivity, placing them in the differential diagnosis of epileptic seizures. Startle syndromes form a heterogeneous group of disorders with three categories: hyperekplexia (HPX), stimulus-induced disorders, and neuropsychiatric syndromes. HPX is characterized by an exaggerated motor startle reflex combined with stiffness and is caused by mutations in different parts of the inhibitory glycine receptor, leading to brainstem pathology. The preserved consciousness distinguishes it from epileptic seizures. Clonazepam is the first-choice therapy. The stimulus-induced disorders cover a broad range of epileptic and nonepileptic disorders, and distinguishing the two can be difficult. Additional information from electroencephalography (EEG) and video registration can help. Many stimulus-induced disorders now have an identified gene defect. Antiepileptic drugs, including benzodiazepines, are frequently mentioned as the best treatment option. Neuropsychiatric syndromes are on the borderland of neurology and psychiatry, and their etiology is poorly understood. These syndromes include startle-induced tics, culture-specific disorders such as Latah, and functional startle syndromes. The electromyography (EMG) startle reflex in these syndromes is characterized by variable recruitment patterns and the presence of a second "orienting" response. Treatment options are limited, but urgently required. In the clinical setting, the patient's history and a (home) video recording together with genetic and electrophysiologic testing help to classify these challenging disorders.
Topics: Humans; Movement Disorders; Reflex, Abnormal; Reflex, Startle; Syndrome
PubMed: 23153204
DOI: 10.1111/j.1528-1167.2012.03709.x -
Brain : a Journal of Neurology Sep 2023Although rigidity is a cardinal motor sign in patients with Parkinson's disease (PD), the instrumental measurement of this clinical phenomenon is largely lacking, and...
Although rigidity is a cardinal motor sign in patients with Parkinson's disease (PD), the instrumental measurement of this clinical phenomenon is largely lacking, and its pathophysiological underpinning remains still unclear. Further advances in the field would require innovative methodological approaches able to measure parkinsonian rigidity objectively, discriminate the different biomechanical sources of muscle tone (neural or visco-elastic components), and finally clarify the contribution to 'objective rigidity' exerted by neurophysiological responses, which have previously been associated with this clinical sign (i.e. the long-latency stretch-induced reflex). Twenty patients with PD (67.3 ± 6.9 years) and 25 age- and sex-matched controls (66.9 ± 7.4 years) were recruited. Rigidity was measured clinically and through a robotic device. Participants underwent robot-assisted wrist extensions at seven different angular velocities randomly applied, when ON therapy. For each value of angular velocity, several biomechanical (i.e. elastic, viscous and neural components) and neurophysiological measures (i.e. short and long-latency reflex and shortening reaction) were synchronously assessed and correlated with the clinical score of rigidity (i.e. Unified Parkinson's Disease Rating Scale-part III, subitems for the upper limb). The biomechanical investigation allowed us to measure 'objective rigidity' in PD and estimate the neuronal source of this phenomenon. In patients, 'objective rigidity' progressively increased along with the rise of angular velocities during robot-assisted wrist extensions. The neurophysiological examination disclosed increased long-latency reflexes, but not short-latency reflexes nor shortening reaction, in PD compared with control subjects. Long-latency reflexes progressively increased according to angular velocities only in patients with PD. Lastly, specific biomechanical and neurophysiological abnormalities correlated with the clinical score of rigidity. 'Objective rigidity' in PD correlates with velocity-dependent abnormal neuronal activity. The observations overall (i.e. the velocity-dependent feature of biomechanical and neurophysiological measures of objective rigidity) would point to a putative subcortical network responsible for 'objective rigidity' in PD, which requires further investigation.
Topics: Humans; Parkinson Disease; Muscle Rigidity; Reflex, Stretch; Reflex, Abnormal; Electromyography
PubMed: 37018058
DOI: 10.1093/brain/awad114 -
Journal of Neuroengineering and... Aug 2020Stiff-Knee gait (SKG) after stroke is often accompanied by decreased knee flexion angle during the swing phase. The decreased knee flexion has been hypothesized to...
BACKGROUND
Stiff-Knee gait (SKG) after stroke is often accompanied by decreased knee flexion angle during the swing phase. The decreased knee flexion has been hypothesized to originate from excessive quadriceps activation. However, it is unclear whether hyperreflexia plays a role in this activation. The goal of this study was to establish the relationship between quadriceps hyperreflexia and knee flexion angle during walking in post-stroke SKG.
METHODS
The rectus femoris (RF) H-reflex was recorded in 10 participants with post-stroke SKG and 10 healthy controls during standing and walking at the pre-swing phase. In order to attribute the pathological neuromodulation to quadriceps muscle hyperreflexia and activation, healthy individuals voluntarily increased quadriceps activity using electromyographic (EMG) feedback during standing and pre-swing upon RF H-reflex elicitation.
RESULTS
We observed a negative correlation (R = - 0.92, p = 0.001) between knee flexion angle and RF H-reflex amplitude in post-stroke SKG. In contrast, H-reflex amplitude in healthy individuals in presence (R = 0.47, p = 0.23) or absence (R = - 0.17, p = 0.46) of increased RF muscle activity was not correlated with knee flexion angle. We observed a body position-dependent RF H-reflex modulation between standing and walking in healthy individuals with voluntarily increased RF activity (d = 2.86, p = 0.007), but such modulation was absent post-stroke (d = 0.73, p = 0.296).
CONCLUSIONS
RF reflex modulation is impaired in post-stroke SKG. The strong correlation between RF hyperreflexia and knee flexion angle indicates a possible regulatory role of spinal reflex excitability in post-stroke SKG. Interventions targeting quadriceps hyperreflexia could help elucidate the causal role of hyperreflexia on knee joint function in post-stroke SKG.
Topics: Adult; Biomechanical Phenomena; Female; Gait Disorders, Neurologic; Humans; Knee Joint; Male; Middle Aged; Quadriceps Muscle; Reflex, Abnormal; Stroke; Walking
PubMed: 32843057
DOI: 10.1186/s12984-020-00724-z