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BACKGROUND Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal disease caused by the change of prion protein (PrP). Affected patients present with rapidly progressive cognitive dysfunction, myoclonus, or akinetic mutism. Diagnosing the Heidenhain variant of sCJD, which initially causes various visual symptoms, can be particularly difficult. CASE REPORT A 72-year-old woman presented with a 2- to 3-month history of photophobia, blurring vision in both eyes. Seven days previously, she showed visual impairment of 20/2000 in both eyes. Left homonymous hemianopia and restricted downward movement of the left eye were observed with an intact pupillary light reflex and normal fundoscopy. On admission, her visual acuity was light perception. Cranial magnetic resonance imaging revealed no abnormality, and electroencephalography showed no periodic synchronous discharges. Cerebrospinal fluid examination on the sixth hospital day revealed tau and 14-3-3 protein with a positive result of real-time quaking-induced conversion. She thereafter developed myoclonus and akinetic mutism and died. Autopsy revealed thinning and spongiform change of the cerebral cortex of the right occipital lobe. Immunostaining showed synaptic-type deposits of abnormal PrP and hypertrophic astrocytes. Consequently, she was diagnosed with the Heidenhain variant of sCJD with both methionine/methionine type 1 and type 2 cortical form based on the western blot of cerebral tissue and PrP gene codon 129 polymorphism. CONCLUSIONS When a patient presents with various progressive visual symptoms, even without typical findings of electroencephalography or cranial magnetic resonance imaging, it is essential to suspect the Heidenhain variant of sCJD and perform appropriate cerebrospinal fluid tests.

Oculopalatal tremor (OPT) is an acquired pathology characterized by continuous and rhythmical soft palatal movements combined with pendular nystagmus. Aside from vascular lesions, oncological masses affecting the dentatorubro-olivary pathway can impair brainstem and/or cerebellar pathways, manifesting as dyssynchronous movement. In this review, we delve into the neurophysiology of OPT along with oncological causes and treatment options based on the most recent clinical trial data. This literature review includes medication treatment data from clinical trials enrolling individuals with features of OPT, including acquired pendular nystagmus (APN). Trials were deemed eligible for inclusion in this review if one or more participants had symptoms determined by the trial authors to be caused by OPT. Trials investigating the treatment of APN secondary to a separate cause, such as multiple sclerosis, were excluded from this review. Several early treatments failed to demonstrate a benefit for patients with APN due to OPT. Trials of anticholinergic agents were largely ineffective and poorly tolerated. Botulinum toxin A demonstrated improvement in APN symptoms. Most recently, trials including memantine and gabapentin have demonstrated success with attenuation of APN. Surgical modalities such as DBS have yet to show improvement, though with only a single case report as evidence. Oculopalatal tremor is a unique manifestation of posterior fossa tumors disrupting the Guillain-Mollaret triangle. Symptom control through medication management has had limited success attributed to poor response and medication intolerance. Surgical modalities like DBS may have an emerging role in OPT treatment by targeting dyssynchronous activity in the dentatorubro-olivary pathway., (© 2021. Belgian Neurological Society.)

Serotonin (5-hydroxytryptamine, 5-HT) plays two important roles in humans-one central and the other peripheral-depending on the location of the 5-HT pools of on either side of the blood-brain barrier. In the central nervous system it acts as a neurotransmitter, controlling such brain functions as autonomic neural activity, stress response, body temperature, sleep, mood and appetite. This role is very important in intensive care, as in critically ill patients multiple serotoninergic agents like opioids, antiemetics and antidepressants are frequently used. High serotonin levels lead to altered mental status, deliria, rigidity and myoclonus, together recognized as serotonin syndrome. In its role as a peripheral hormone, serotonin is unique in controlling the functions of several organs. In the gastrointestinal tract it is important for regulating motor and secretory functions. Apart from intestinal motility, energy metabolism is regulated by both central and peripheral serotonin signaling. It also has fundamental effects on hemostasis, vascular tone, heart rate, respiratory drive, cell growth and immunity. Serotonin regulates almost all immune cells in response to inflammation, following the activation of platelets.

Acid ceramidase deficiency is an orphan lysosomal disorder caused by ASAH1 pathogenic variants and presenting with either Farber disease or spinal muscle atrophy with progressive myoclonic epilepsy (SMA-PME). Phenotypic and genotypic features are rarely explored beyond the scope of case reports. Furthermore, the new biomarker C26-Ceramide requires validation in a clinical setting. We evaluated the clinical, biomarker and genetic spectrum of 15 Egyptian children from 14 unrelated families with biallelic pathogenic variants in ASAH1 (12 Farber and 3 SMA-PME). Recruited children were nine females/six males ranging in age at diagnosis from 13 to 118 months. We detected ASAH1 pathogenic variants in all 30 alleles including three novel variants (c.1126A>G (p.Thr376Ala), c.1205G>A (p.Arg402Gln), exon-5-deletion). Both total C26-Ceramide and its trans- isomer showed 100% sensitivity for the detection of ASAH1-related disorders in tested patients. A 10-year-old girl with the novel variant c.1205G>A (p.Arg402Gln) presented with a new peculiar phenotype of PME without muscle atrophy. We expanded the phenotypic spectrum of ASAH1-related disorders and validated the biomarker C26-Ceramide for supporting diagnosis in symptomatic patients., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Myoclonus-dystonia is an early onset genetic disorder characterised by subcortical myoclonus and less prominent dystonia. Its primary causative gene is the epsilon-sarcoglycan gene but the syndrome of "myoclonic dystonia" has been shown to be a heterogeneous group of genetic disorders. The underlying pathophysiology of myoclonus-dystonia is incompletely understood, although it may relate to dysfunction of striatal monoamine neurotransmission or disruption of cerebellothalamic networks (possibly via a GABAergic deficit of Purkinje cells). A broad range of oral medical therapies have been used in the treatment of myoclonus-dystonia with a varying response, and limited data relating to efficacy and tolerability, yet this condition responds dramatically to alcohol. Few well conducted randomized controlled trials have been undertaken leading to an empirical ad hoc approach for many patients. We review the current evidence for pharmacological therapies in myoclonus-dystonia, discuss implications for underlying pathogenesis of the condition and propose a treatment algorithm for these patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: Funding: None. Conflicts of Interest: The authors report no conflicts of interest. Ethics Statement: All patients who appear on the video have provided written informed consent and authorization for videotaping and publication of the videotape.

Background: Abnormal sensory processing, including temporal discrimination threshold, has been described in various dystonic syndromes., Objective: To investigate visual sensory processing in DYT-SGCE and identify its structural correlates., Methods: DYT-SGCE patients without DBS (DYT-SGCE-non-DBS) and with DBS (DYT-SGCE-DBS) were compared to healthy volunteers in three tasks: a temporal discrimination threshold, a movement orientation discrimination, and movement speed discrimination. Response times attributed to accumulation of sensory visual information were computationally modelized, with μ parameter indicating sensory mean growth rate. We also identified the structural correlates of behavioral performance for temporal discrimination threshold., Results: Twenty-four DYT-SGCE-non-DBS, 13 DYT-SGCE-DBS, and 25 healthy volunteers were included in the study. In DYT-SGCE-DBS, the discrimination threshold was higher in the temporal discrimination threshold (P = 0.024), with no difference among the groups in other tasks. The sensory mean growth rate (μ) was lower in DYT-SGCE in all three tasks (P < 0.01), reflecting a slower rate of sensory accumulation for the visual information in these patients independent of DBS. Structural imaging analysis showed a thicker left primary visual cortex (P = 0.001) in DYT-SGCE-non-DBS compared to healthy volunteers, which also correlated with lower μ in temporal discrimination threshold (P = 0.029). In DYT-SGCE-non-DBS, myoclonus severity also correlated with a lower μ in the temporal discrimination threshold task (P = 0.048) and with thicker V1 on the left (P = 0.022)., Conclusion: In DYT-SGCE, we showed an alteration of the visual sensory processing in the temporal discrimination threshold that correlated with myoclonus severity and structural changes in the primary visual cortex. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

A 65-year-old man presented with transient neurological symptoms, followed by rapid cognitive decline, myoclonus and fevers. He had evidence of scleritis and an arthropathy. This paper reports the clinicopathological conference discussed at the Association of British Neurologists Annual Meeting 2017., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cerebellar Purkinje cell axonal degeneration has been identified in horses with shivering but its relationship with abnormal hindlimb movement has not been elucidated., Objectives: To characterise surface electromyographic (sEMG) hindlimb muscle activity in horses with shivering, correlate with clinical scores and examine horses for Purkinje axonal degeneration., Study Design: Descriptive controlled clinical study., Methods: The hindlimb of seven shivering and six control draught horses were clinically scored. Biceps femoris (BF), vastus lateralis (VL), tensor fasciae latae and extensor digitorum longus were recorded via sEMG during forward/backward walking and trotting. Integrated (iEMG) and peak EMG activity were compared between groups and correlated with clinical locomotor exam scores. Sections of the deep cerebellar nuclei (DCN) of six of the seven shivering horses were examined with calbindin immunohistochemistry., Results: In control horses, backward walking resembled forward walking (right hindlimb peak EMG: backward: 47.5 ± 21.9%, forward: 36.9 ± 15.7%) but displayed significantly higher amplitudes during trotting (76.1 ± 3.4%). However, in shivering horses, backward walking was significantly different from forward (backward: 88.5 ± 21.5%, forward: 49.2 ± 8.9%), and resembled activity during trotting (81.4 ± 4.8%). Specific to backward walking, mean sEMG amplitude fell outside two standard deviations of mean control sEMG for ≥25% of the stride in the BF for all seven and the VL for six of the seven shivering horses. Locomotor exam scores were correlated with peak EMG (r = 0.87) and iEMG (r = 0.87). Calbindin-positive spheroids were present in Purkinje axons in DCN of all shivering horses examined., Main Limitations: The neuropathological examination focused specifically on the DCN and, therefore, we cannot fully exclude additional lesions that may have influenced abnormal sEMG findings in shivering horses., Conclusion: Shivering is characterised by abnormally elevated muscle recruitment particularly in BF and VL muscles during backward walking and associated with selective Purkinje cell distal axonal degeneration., (© 2018 EVJ Ltd.)

Subacute sclerosing panencephalitis is a late complication of measles infection and develops usually 6 to 15 years after the primary measles infection. Fulminant subacute sclerosing panencephalitis is an infrequently encountered form wherein the disease rapidly progresses to death. A six-year old male child presented with fever, abnormal movements of the left side of body followed by weakness of the left side of the body, and involuntary abnormal movements of right upper and lower limbs. On examination, he was drowsy and was unable to communicate. He had right-sided hemiballismus. He also had left-sided hemiparesis and the left plantar reflex was extensor. Cerebrospinal fluid examination revealed elevated protein and cells. In the serum and cerebrospinal fluid, anti-measles IgG antibodies were found to be positive. No other viral marker was noted in the cerebrospinal fluid. Magnetic resonance imaging of the brain showed extensive damage to the right temporal, parietal, and to a lesser extent, the frontal region as well as subcortical structures of these regions. Electroencephalography revealed generalized slowing of waves. Over a period of the next 3 days, the intensity and frequency of choreiform movements markedly reduced and the patient developed periodic generalized myoclonus, which was predominantly present on the right side. The patient succumbed to his illness and died after one month. Fulminant subacute sclerosing panencephalitis may have unusual clinical manifestations such as hemiballismus. In fulminant subacute sclerosing panencephalitis, neuroimaging may show extensive cortical damage.

Multiple sclerosis (MS) is considered a primary autoimmune disease; however, this view is increasingly being challenged in basic and clinical science arenas because of the growing body of clinical trials' data showing that exclusion of immune cells from the CNS only modestly slows disease progression to disability. Accordingly, there is significant need for expanding the scope of potential disease mechanisms to understand the etiology of MS. Concomitantly, the use of a broader range of pre-clinical animal models for characterizing existing efficacious clinical treatments may elucidate additional or unexpected mechanisms of action for these drugs that augment insight into MS etiology. Herein, we explore the in vivo mechanism of action of dimethyl fumarate, which has been shown to suppress oxidative stress and immune cell responses in psoriasis and MS. Rather than studying this compound in the context of an experimental autoimmune-induced attack on the CNS, we have used a genetic model of hypomyelination, male rumpshaker (rsh) mice, which exhibit oligodendrocyte metabolic stress and startle-induced subcortical myoclonus during development and into adulthood. We find that myoclonus is reduced 30-50% in treated mutants but we do not detect substantial changes in metabolic or oxidative stress response pathways, cytokine modulation, or myelin thickness (assessed by anova). All procedures involving vertebrate animals in this study were reviewed and approved by the IACUC committee at Wayne State University., (© 2017 International Society for Neurochemistry.)

Background: Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear. In this paper we present eight Dutch cases of NP-C of whom five with myoclonus., Methods: Eight patients with genetically confirmed NP-C were recruited from two Dutch University Medical Centers. A structured interview and neuropsychological tests (for working and verbal memory, attention and emotion recognition) were performed. Movement disorders were assessed using a standardized video protocol. Quality of life was evaluated by questionnaires (Rand-36, SIP-68, HAQ). In four of the five patients with myoclonic jerks simultaneous EEG with EMG was performed., Results: A movement disorder was the initial neurological symptom in six patients: three with myoclonus and three with ataxia. Two others presented with psychosis. Four experienced cognitive deficits early in the course of the disease. Patients showed cognitive deficits in all investigated domains. Five patients showed myoclonic jerks, including negative myoclonus. In all registered patients EEG-EMG coherence analysis and/or back-averaging proved a cortical origin of myoclonus. Patients with more severe movement disorders experienced significantly more physical disabilities., Conclusions: Presenting neurological symptoms of NP-C include movement disorders, psychosis and cognitive deficits. At current neurological examination movement disorders were seen in all patients. The incidence of myoclonus in our cohort was considerably higher (63 %) than in previous publications and it was the presenting symptom in 38 %. A cortical origin of myoclonus was demonstrated. Our data suggest that myoclonus may be overlooked in patients with NP-C. All patients scored significantly lower on physical domains of HRQoL. Symptomatic treatment of movement disorders may improve physical functioning and subsequently HRQoL.

Background: Subacute sclerosing panencephalitis is a devastating neurodegenerative disease with a characteristic clinical course. Atypical presentations may be seen in 10% of the cases., Aims: To describe the atypical clinical and radiological features of SSPE in a child form endemic country., Methods: A 5-year-old boy presented with acute-onset cerebellar ataxia without associated encephalopathy, focal motor deficits, seizures or cognitive decline. He had varicella-like illness with vesicular, itchy truncal rash erupting one month prior to the onset of these symptoms. He underwent detailed neurological assessment, relevant laboratory and radiological investigations., Results: Neuroimaging revealed peculiar brain stem lesions involving the pons and cerebellum suggestive of demyelination. With a presumptive diagnosis of clinically isolated syndrome of demyelination, he was administered pulse methylprednisolone (30 mg/kg/day for 5 days). Four weeks later he developed myoclonic jerks. Electroencephalogram showed characteristic periodic complexes time-locked with myoclonus. CSF and serum anti-measles antibody titres were elevated (1:625)., Conclusion: Our report highlights that subacute sclerosing panencephalitis can present atypically as isolated acute cerebellar ataxia and peculiar involvement of longitudinal and sparing of transverse pontine fibres. The predominant brainstem abnormalities in the clinical setting may mimick acute demyelinating syndrome. Hence, it is important to recognize these features of subacute sclerosing panencephalitis in children, especially in the endemic countries., (Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

"Shivers" is a progressive equine movement disorder of unknown etiology. Clinically, horses with shivers show difficulty walking backward, assume hyperflexed limb postures, and have hind limb tremors during backward movement that resembles shivering. At least initially, forward movements are normal. Given that neither the neurophysiologic nor the pathologic mechanisms of the disease is known, nor has a neuroanatomic locus been identified, we undertook a detailed neuroanatomic and neuropathologic analysis of the complete sensorimotor system in horses with shivers and clinically normal control horses. No abnormalities were identified in the examined hind limb and forelimb skeletal muscles nor the associated peripheral nerves. Eosinophilic segmented axonal spheroids were a common lesion. Calretinin-positive axonal spheroids were present in many regions of the central nervous system, particularly the nucleus cuneatus lateralis; however, their numbers did not differ significantly from those of control horses. When compared to controls, calretinin-negative, calbindin-positive, and glutamic acid decarboxylase-positive spheroids were increased 80-fold in Purkinje cell axons within the deep cerebellar nuclei of horses with shivers. Unusual lamellar or membranous structures resembling marked myelin decompaction were present between myelin sheaths of presumed Purkinje cell axons in the deep cerebellar nuclei of shivers but not control horses. The immunohistochemical and ultrastructural characteristics of the lesions combined with their functional neuroanatomic distribution indicate, for the first time, that shivers is characterized by end-terminal neuroaxonal degeneration in the deep cerebellar nuclei, which results in context-specific hypermetria and myoclonus., (© The Author(s) 2015.)

Scorpionism is a public health problem in many tropical countries, especially in North Africa, South India, Latin America and the Middle East. In Brazil, patients with severe scorpion envenoming have mainly cardiovascular events, including acute heart failure, acute respiratory distress syndrome and shock, death is rare. We described 58 accidents presumably caused by Tityus obscurus in Brazilian Amazonia. Patients reported a sensation of "electric shocks" which could last hours. The vast majority of patients presented a clinical picture compatible with acute cerebellar dysfunction, beginning minutes and lasting up to 2 days after the accident. They presented cerebellar ataxia, dysdiadochokinesia, dysmetry, dysarthria, dyslalia, nausea and vomiting. Besides, some patients presented myoclonus and fasciculation which can also be attributed to cerebellar dysfunction or maybe the result of direct action on skeletal muscle. Two patients had evidence of intense rhabdomyolysis and acute kidney injury. The clinical picture in this scorpion envenoming is mainly characterized by an acute dysfunction of cerebellar activities and abnormal neuromuscular manifestations and in some cases muscle injury which are not described in any other region of the world. This work presents clinical, epidemiologic, laboratory and treatment aspects of this unmatched scorpion envenoming in the state of Pará, northern Brazil., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To clarify the neurophysiologic mechanism of epileptic negative myoclonus (ENM), we analyzed the magnetoencephalography (MEG) of a patient with ENM., Methods: The 52-year-old right-handed male had frequent ENM in the right upper limb during awake and monthly seizures with sudden tonic stiffening of the right forearm during sleep. MRI demonstrated a focal cortical dysplasia in the cortex of the posterior portion of the left superior frontal sulcus. Whole-head type MEG, electroencephalography and electromyography were simultaneously recorded during ENM. Single equivalent currents dipoles (ECDs) were calculated for each spike component followed by silent period (SP) in the right deltoid muscle. These MEG spike components were averaged with respect to their peaks, and single ECD was also calculated for the averaged spike component. Furthermore, we analyzed the MEG with the silent-period-locked-averaging (SPLA) method. Twenty MEG signal data were averaged with respect to the onset of SP. Twenty epochs in each of five separate periods of recording were repeatedly averaged. ECDs were calculated for spike components observed in each averaged epoch., Results: ECDs of each spike followed by SP were clustered near the cortex of the left central sulcus. In MEG spike averaging and SPLA method, ECDs at the peak of spike components were located near the right shoulder division of the primary sensorimotor cortex reproducibly. ECDs on the ascending phase before the peak were located lateral to the above ECD location in MEG spike averaging method., Conclusions: ENM was produced by an inhibitory action on the primary sensorimotor cortex corresponding to the body segment in which ENM occurs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Jaw clonus is an uncommon pathological reflex thought to indicate corticospinal tract dysfunction above the Vth cranial nerve. It is useful as a sign of upper motor neuron dysfunction above the spinal cord. One theory of self excitation posits an inverse and linear relationship between clonus frequency and the length of the reflex arc, to explain the higher frequency of clonus in the ankles than the wrist. Only two previous cases of jaw clonus have been published. One of these plus the present case suggest that an inverse and linear relationship is not correct.

Background: Approximately half of Japanese sporadic Creutzfeldt-Jakob disease (sCJD) cases show panencephalopathic-type (PE-type) pathology, which is a rare subtype in North Americans and Europeans. Until now, the differences in the clinical course between subacute spongiform encephalopathy (SSE) cases and PE-type cases have been unclear., Methods: To investigate the clinical course of both subtypes, clinical findings from 42 Japanese MM1-type sCJD cases (20 SSE cases and 22 PE-type cases) were retrospectively evaluated by statistical analysis., Results: No significant differences could be found regarding age at disease onset, the period between disease onset and first observation of myoclonus, the period between disease onset and the first observation of periodic sharp-wave complexes on electroencephalogram, or the period between disease onset and progression to the akinetic mutism state - whereas total disease duration and the period between the akinetic mutism state and death were significantly longer in PE-type cases. The prolonged disease duration was induced by the extended survival period in the akinetic mutism state. There was a statistically significant difference between the two series regarding performance of tube-feeding, but no statistically significant difference regarding performance of tracheotomy or gastrostomy. None of the cases received mechanical ventilation., Conclusion: We speculate that the most crucial factor of the prolonged survival period of Japanese sCJD cases, particularly in the PE-type, is that the introduction of tube-feeding in the akinetic mutism state leads to the stabilization of the patient's general condition., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A 71-year-old woman presented with acute inferior homonymous quadrantanopia initially mimicking acute ischemic stroke. As clinical signs and symptoms progressed to akinetic mutism with myoclonus the diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease was made. Brain MRI 4 days after symptom onset revealed ribbon-like high signal intensity in the medial occipital cortex., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The putative involvement of the cerebellum in the pathogenesis of cortical myoclonic syndromes has been long hypothesized, as neuropathological changes in patients with cortical myoclonus have most commonly been found in the cerebellum rather than in the suspected culprit, the primary somatosensory cortex. A model of increased cortical excitability due to loss of cerebellar inhibitory control via cerebello-thalamo-cortical connections has been proposed, but evidence remains equivocal. Here, we explore this hypothesis by examining syndromes that present with cortical myoclonus and ataxia. We first describe common clinical characteristics and underlying neuropathology. We critically view information on cerebellar physiology with regard to motorcortical output and compare findings between hypothesized and reported neurophysiological changes in conditions with cortical myoclonus and ataxia. We synthesize knowledge and focus on neurochemical changes in these conditions. Finally, we propose that the combination of alterations in inhibitory neurotransmission and the presence of cerebellar pathology are important elements in the pathogenesis of cortical myoclonus., (© 2014 International Parkinson and Movement Disorder Society.)

Purpose of Review: Oculopalatal tremor (OPT) is an acquired disorder resulting from the interruption of a specific brainstem circuitry, the dentato-rubro-olivary pathway or Guillain-Mollaret triangle. The recent literature on OPT and olivary hypertrophy was reviewed with specific interest regarding causes, diagnostic procedures, physiopathology and therapies., Recent Findings: OPT is associated with inferior olivary hypertrophy, and recent findings have provided a better understanding of its intimate mechanisms. A dual-mechanism model, combining an oscillator (inferior olive) and a modulator/amplifier (cerebellum), best explains the development of OPT. Electrotonic coupling and specific Ca channels contribute to oscillations of inferior olivary nucleus neurons in OPT. Improvement of visual symptoms can be achieved with oral gabapentin or memantine., Summary: Both the neuronal circuitry and the physiopathology of OPT are now better understood. This opens up an era of specific therapy for this rare cause of disabling oscillopsia.

l-2 hydroxyglutaric aciduria is a rare, autosomal recessively inherited metabolic disorder of organic acid metabolism. A 5-year-old boy presented with eyelid myoclonia with absences that proved difficult to control with first-line anticonvulsants. An electroencephalogram produced profoundly abnormal results, with generalized spike-and-wave discharges. The patient became seizure-free with a combination therapy of clonazepam, levetiracetam, and lamotrigine. Magnetic resonance imaging demonstrated subcortical white matter and basal ganglia alterations. Urinary organic acid analysis demonstrated increased excretion of l-2 hydroxyglutaric acid. Although rare, seizures can occur as a presenting sign of slowly progressing organic acidurias, e.g., l-2 hydroxyglutaric aciduria. Both eyelid myoclonia with absences and l-2 hydroxyglutaric aciduria comprise rare disorders. To our knowledge, this case report is the first of l-2 hydroxyglutaric aciduria presenting with symptomatic eyelid myoclonia with absences., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The syndrome of progressive encephalopathy with limb rigidity has been historically termed progressive encephalomyelitis with rigidity and myoclonus (PERM) or stiff-person syndrome plus., Methods: The case is presented of a previously healthy 28-year-old man with a rapidly fatal form of PERM developing over 2 months., Results: Serum antibodies to both NMDA receptors (NMDAR) and glycine receptors (GlyR) were detected postmortem, and examination of the brain confirmed an autoimmune encephalomyelitis, with particular involvement of hippocampal pyramidal and cerebellar Purkinje cells and relative sparing of the neocortex. No evidence for an underlying systemic neoplasm was found., Conclusion: This case displayed not only the clinical features of PERM, previously associated with GlyR antibodies, but also some of the features associated with NMDAR antibodies. This unusual combination of antibodies may be responsible for the particularly progressive course and sudden death.

Background: We report 3 patients with typical clinical and electrophysiological characteristics of propriospinal myoclonus propagating from a thoracic spine generator., Methods: In these patients, the pattern of recruitment of long-latency electromyographic reflexes in abdominal muscles was studied in response to various stimuli., Results: Abdominal reflex latency varied from 60 to 140 ms depending on stimulus location. Latency increased from magnetic stimulation of the thoracic spine to electrical stimulation of the supraorbital nerve, electrical stimulation of the median nerve, and magnetic stimulation of the motor cortex., Conclusions: Long-latency abdominal reflex jerks are probably controlled by the brain stem to propriospinal system projections in patients with propriospinal myoclonus. The stereotyped pattern of recruitment of these reflexes could be of clinical utility to differentiate organic propriospinal myoclonus from psychogenic or mimicked jerks., (Copyright © 2011 Movement Disorder Society.)

The ability to understand how Parkinson's disease neurodegeneration leads to cortical dysfunction will be critical for developing therapeutic advances in Parkinson's disease dementia. The overall purpose of this project was to study the small-amplitude cortical myoclonus in Parkinson's disease as an in vivo model of focal cortical dysfunction secondary to Parkinson's disease neurodegeneration. The objectives were to test the hypothesis that cortical myoclonus in Parkinson's disease is linked to abnormal levels of α-synuclein in the primary motor cortex and to define its relationship to various biochemical, clinical, and pathological measures. The primary motor cortex was evaluated for 11 Parkinson's disease subjects with and 8 without electrophysiologically confirmed cortical myoclonus (the Parkinson's disease + myoclonus group and the Parkinson's disease group, respectively) who had premortem movement and cognitive testing. Similarly assessed 9 controls were used for comparison. Measurements for α-synuclein, Aβ-42 peptide, and other biochemical measures were made in the primary motor cortex. A 36% increase in α-synuclein was found in the motor cortex of Parkinson's disease + myoclonus cases when compared with Parkinson's disease without myoclonus. This occurred without significant differences in insoluble α-synuclein, phosphorylated to total α-synuclein ratio, or Aβ-42 peptide levels. Higher total motor cortex α-synuclein levels significantly correlated with the presence of cortical myoclonus but did not correlate with multiple clinical or pathological findings. These results suggest an association between elevated α-synuclein and the dysfunctional physiology arising from the motor cortex in Parkinson's disease + myoclonus cases. Alzheimer's disease pathology was not associated with cortical myoclonus in Parkinson's disease. Cortical myoclonus arising from the motor cortex is a model to study cortical dysfunction in Parkinson's disease., (Copyright © 2011 Movement Disorder Society.)

Background: Lewy body syndromes (mainly Parkinson's disease and dementia with Lewy bodies) share many clinical features and usually have a slowly progressive course. Some patients may show rapid symptoms progression., Objective: To evaluate clinical and neuropathological features of patients with a rapidly progressive diffuse Lewy Body disease., Methods: Review clinical records and pathological findings of 6 cases with diffuse Lewy Body disease and rapid disease progression (less than 18 months before death)., Results: Mean age at disease onset was 72.5 years, and mean disease duration was 9 months. Onset consisted of delirium in 3 patients and rapidly progressive dementia in the other three. All cases presented visual hallucinations and delusions; cognitive symptoms were fluctuating in two, parkinsonism occurred in four, and myoclonus in three. Brain MRI did not show cortical or basal ganglia hyperintensities. Periodic sharp waves were absent on EEG. 14.3.3 protein in CSF was negative. Myocardial (123) I-metaiodo-benzyl-guanidine SPECT showed marked reduction in tracer uptake in the 2 patients tested. Neuropathological studies did not identify any particular feature that could differentiate rapidly progressive diffuse Lewy body disease from classical diffuse Lewy body disease., Conclusions: Diffuse Lewy body disease is a possible cause of rapidly progressive dementia and should be included in the differential diagnosis of confusional states of undetermined cause. In patients with rapidly progressive dementia, the presence of fluctuating cognition, parkinsonism, hallucinations, delusions, or severe dysautonomia, should raise the suspicion of diffuse Lewy body disease. Neuroimaging studies such as (123) I-metaiodo-benzyl-guanidine myocardial scintigraphy may support the clinical diagnosis of diffuse Lewy body disease. © 2011 Movement Disorder Society., (Copyright © 2011 Movement Disorder Society.)

This review examines some of the advances in understanding myoclonus over the last 25 years. The classification of myoclonus into cortical, brainstem, and spinal forms has been consolidated, each with distinctive clinical characteristics and physiological mechanisms. New genetic causes of myoclonus have been identified, and the molecular basis of several of these conditions has been discovered. It is increasingly apparent that disease of the cerebellum is particularly important in the genesis of cortical reflex myoclonus. However, the precise mechanism and origin of myoclonus in many situations remain uncertain. Effective treatment of myoclonus remains limited, and the challenge lies ahead to develop more therapeutic options., (Copyright © 2011 Movement Disorder Society.)

Background: Abnormally enhanced cortical rhythmic activities have been reported in patients with cortical myoclonus. We recently reported a new triad-conditioning transcranial magnetic stimulation (TMS) method to detect the intrinsic rhythms of the primary motor cortex (M1). Triad-conditioning TMS revealed a 40-Hz intrinsic rhythm of M1 in normal subjects. In this investigation, we study the motor cortical facilitation induced by rhythmic triple TMS pulses (triad-conditioning TMS) in patients with cortical myoclonus., Methods: Subjects were 7 patients with cortical myoclonus (28-74 years old) and 13 healthy volunteers (30-71 years old). Three conditioning stimuli over M1 at the intensity of 110% active motor threshold preceded the test TMS at various interstimulus intervals corresponding to 10-200 Hz. The resulting amplitudes of conditioned motor evoked potentials recorded from the contralateral hand muscle were compared with those evoked by the test stimulus alone., Results: The facilitation at 25 ms (40 Hz) observed in normal subjects was absent in patients with cortical myoclonus. Instead, triad-conditioning TMS induced facilitation at a 40 ms interval (25 Hz) in cortical myoclonus., Discussions: This change in the timing of facilitation may be explained by a shift of the most preferential intrinsic rhythm of M1, or by some dysfunction in the interneuronal network in cortical myoclonus., (Copyright © 2011 Movement Disorder Society.)

Background: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive fatal central nervous system disorder, which consists of three main catalogues: sporadic, familial, and iatrogenic CJD., Methodology/principal Findings: In China, the surveillance for CJD started in 2006, covering 12 provincial Centers for Disease Control and Prevention (CDCs) and 15 hospitals. From 2006 to 2010, 624 suspected patients were referred to China CJD surveillance. The epidemiological, clinical and laboratory features of sporadic CJD (sCJD) were analysed. Both groups of probable and possible sCJD showed highest incidences in the population of 60 to 69 year-olds. The most common presenting symptoms were progressive dementia and mental-related symptoms (neurological symptoms including sleeping turbulence, depression, anxiety and stress). Among the four main clinical manifestations, myoclonus was more frequently observed in the probable sCJD patients. About 2/3 of probable sCJD cases showed positive 14-3-3 in CSF and/or periodic sharp wave complexes (PSWC) in electroencephalography (EEG). The presence of myoclonus was significantly closely related with the appearance of PSWC in EEG. Polymorphisms of codon 129 in PRNP of the notified cases revealed a highly predominant M129M genotype in Han Chinese. Among 23 genetic human prion diseases, ten were D178N/M129M Fatal familial insomnia (FFI) and five were T188K genetic CJD (gCJD), possibly indicating a special distribution of gCJD-related mutations in Han Chinese., Conclusion: From the period of 2006 to 2010, 261 patients were diagnosed as sCJD and 23 patients were diagnosed as genetic human prion diseases in China. The epidemiological, clinical and laboratory analysis data were consistent with the characteristics of sporadic CJD, which provide insight into the features of CJD in China.

A 19-month-old girl presented with progressive myoclonic jerking of both proximal lower extremities. On her brain magnetic resonance imaging (MRI), the authors found an ill-defined mass involving cerebellar vermis and the right middle cerebellar peduncle. ( 11)C-methionine positron emission tomography (PET) showed no abnormalities, but (18)F-fluorodeoxyglucose ((18)F-FDG) PET revealed a well-defined hypermetabolic focus. Depth electrodes were inserted deep into the mass, which recorded focal slow waves associated with the clinical myoclonus. Following the removal of the tumor, the myoclonus was completely resolved with no neurological deficit. Here, the authors present a case showing progressive myoclonus associated with a cerebellar ganglioglioma with the electrophysiological data, which provides strong supportive evidence that the cerebellum can be a myoclonus generator.