Search

Lesions in the Guillain–Mollaret (G–M) triangle frequently cause various types of tremors or tremor-like movements. Nevertheless, we know relatively little about their generation mechanisms. The deep cerebellar nuclei (DCN), which is a primary node of the triangle, has two main output paths: the primary excitatory path to the thalamus, the red nucleus (RN), and other brain stem nuclei, and the secondary inhibitory path to the inferior olive (IO). The inhibitory path contributes to the dentato-olivo-cerebellar loop (the short loop), while the excitatory path contributes to the cerebrocerebellar loop (the long loop). We propose a novel hypothesis: each loop contributes to physiologically distinct type of tremors or tremor-like movements. One type of irregular tremor-like movement is caused by a lesion in the cerebrocerebellar loop, which includes the primary path. A lesion in this loop affects the cerebellar forward model and deteriorates its accuracy of prediction and compensation of the feedback delay, resulting in irregular instability of voluntary motor control, i.e., cerebellar ataxia (CA). Therefore, this type of tremor, such as kinetic tremor, is usually associated with other symptoms of CA such as dysmetria. We call this type of tremor forward model-related tremor. The second type of regular tremor appears to be correlated with synchronized oscillation of IO neurons due, at least in animal models, to reduced degrees of freedom in IO activities. The regular burst activity of IO neurons is precisely transmitted along the cerebellocerebral path to the motor cortex before inducing rhythmical reciprocal activities of agonists and antagonists, i.e., tremor. We call this type of tremor IO-oscillation-related tremor. Although this type of regular tremor does not necessarily accompany ataxia, the aberrant IO activities (i.e., aberrant CS activities) may induce secondary maladaptation of cerebellar forward models through aberrant patterns of long-term depression (LTD) and/or long-term potentiation (LTP) of the cerebellar circuitry. Although our hypothesis does not cover all tremors or tremor-like movement disorders, our approach integrates the latest theories of cerebellar physiology and provides explanations how various lesions in or around the G–M triangle results in tremors or tremor-like movements. We propose that tremor results from errors in predictions carried out by the cerebellar circuitry.

Background: Human immunodeficiency viruses (HIV) infection is associated with a broad range of neurological manifestations, including opsoclonus-myoclonus ataxia syndrome (OMAS) occurring in primary infection, immune reconstitution syndrome or in case of opportunistic co-infection.Case: We report the exceptional case of a 43-year-old female under HIV treatment for 10 years who presented initially with suspected epileptic seizure. Although the clinical picture slightly improved under anti-epileptic treatment, it was rapidly attributed to OMAS. The patient exhibited marked opsoclonus, mild dysarthria, upper limbs intermittent myoclonus, ataxia in 4 limbs, truncal ataxia, and a severe gait ataxia (SARA score: 34). The diagnostic work-up showed radiological and biological signs of central nervous system (CNS) inflammation and cerebral venous sinus thromboses. The HIV viral load was higher in cerebrospinal fluid (CSF) than in the blood (4,560 copies/ml vs. 76 copies/ml). She was treated for 5 days with pulsed corticotherapy. Dolutegravir and anticoagulation administration were initiated. Follow-ups at 2 and 4 months showed a dramatic improvement of clinical neurologic status (SARA score at 4 months: 1), reduction of CNS inflammation and revealed undetectable CSF and serum viral loads.Conclusion: This case underlines the importance of the evaluation of the CSF viral load in HIV patients developing OMAS and suggests CSF HIV RNA escape as a novel cause for OMAS.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the cause of the current pandemic coronavirus disease 2019 (COVID-19), primarily targets the respiratory system. Some patients also experience neurological signs and symptoms ranging from anosmia, ageusia, headache, nausea, and vomiting to confusion, encephalitis, and stroke. Approximately 36% of those with severe COVID-19 experience neurological complications. The virus may enter the central nervous system through the olfactory nerve in the nasal cavity and damage neurons in the brainstem nuclei involved in the regulation of respiration. Patients with cerebellar ataxia (CA) are particularly vulnerable to severe outcome if they contract COVID-19 because of the complexity of their disease, the presence of comorbidities, and their use of immunosuppressive therapies. Most CA patients burdened by progressive neurologic deficits have substantially impaired mobility and other essential functions, for which they rely heavily on ambulatory services, including rehabilitation and psychosocial care. Cessation of these interventions because of isolation restrictions places the CA patient population at risk of further deterioration. This international panel of ataxia experts provides recommendations for neurologists caring for patients with CA, emphasizing a pro-active approach designed to maintain their autonomy and well-being: continue long-term medications, promote rehabilitation efforts, utilize the technology of virtual visits for regular contact with healthcare providers, and pay attention to emotional and psychosocial health. Neurologists should play an active role in decision-making in those CA cases requiring escalation to intensive care and resuscitation. Multi-disciplinary collaboration between care teams is always important, and never more so than in the context of the current pandemic.

Current assessment of patients with cerebellar disorders is based on conventional neurological examination that is dependent on subjective judgements. Quantitative measurement of cerebellar ataxias (CAs) is essential for assessment of evidence-based treatments and the monitoring of the progress or recovery of diseases. It may provide us a useful tool to navigate future treatments for ataxia. We developed a Kinect v2. sensor system with a novel algorithm to measure and evaluate movements for two tests of Scale for the Assessment and Rating of Ataxia (SARA): the nose-finger test and gait. For the nose-finger test, we evaluated and compared accuracy, regularities and smoothness in the movements of the index finger and the proximal limbs between cerebellar patients and control subjects. For the task of walking, we evaluated and compared stability between the two groups. The precision of the system for evaluation of movements was smaller than 2 mm. For the nose-finger test, the mildly affected patients tended to show more instability than the control subjects. For a severely affected patient, our system quantified the instability of movements of the index finger using kinematic parameters, such as fluctuations and average speed. The average speed appears to be the most sensitive parameter that contrasts between patients with CAs and control subjects. Furthermore, our system also detected the adventitious movements of more proximal body parts, such as the elbow, shoulder and head. Assessment of walking was possible only in patients with mild CAs. They demonstrated large sways and compensatory wide stances. These parameters appeared to show higher accuracy than SARA. This examiner-independent device measures movements of the points of interest of SARA more accurately than eye and further provides additional information about the ataxic movements (e.g., the adventitious movements of the elbow, shoulder and head in the nose-finger test and the wide-based walking with large oscillation in the gait task), which is out of the scope of SARA. Our new system enables more accurate scoring of SARA and further provides additional information that is not currently evaluated with SARA. Therefore, it provides an easier, more accurate and more systematic description of CAs.

Posterior reversible encephalopathy syndrome (PRES) is a potentially severe disorder of the autoregulation of cerebral perfusion. The major clinical manifestations are headache, seizures, altered mental status, and visual loss. The typical radiological finding is vasogenic edema predominating in the white matter of occipital and parietal lobes. PRES is increasingly recognized as a clinico-radiological entity owing to improvements and fast availability of brain imaging, especially magnetic resonance imaging (MRI). We present the exceptional case of a 67-year-old female patient with a gastric adenocarcinoma at stage IIB (T3N0M0) treated by FLOT chemotherapy (5-fluorouracil, oxaliplatin, docetaxel, and folinic acid). Two months after the unique administration of FLOT regimen, she developed sudden posterior headache and visual loss. Blood pressure values were normal. Cerebral tomography showed ischemic-like occipital bilateral lesions, and angiographic sequences revealed breakdown of the blood–brain barrier (BBB). MRI revealed bilateral parieto-occipital T1 hypointensity and T2 hyperintensity, which demonstrated vasogenic edema. The rest of the parts of the lesions were T1 hyperintensity, T2 hyperintensity, and diffusion-weighted imaging (DWI) hyperintensity, which indicate cortical laminar necrosis. After injection of gadolinium, a linear enhancement of the cortex was observed. She was treated with oral nimodipine. Follow-up was characterized by permanent visual sequelae and tetraparesis. PRES represents an urgent neurological condition. Our observation highlights that PRES should be considered in patients under chemotherapy, even when their blood pressure remains within normal range. This is the first report of PRES triggered by FLOT chemotherapy and with a silent window of 2 months between chemotherapy and PRES, widening further the spectrum of chemotherapy-induced PRES. Our case highlights the potential role of FLOT regimen in the pathogenesis of PRES and the need for a novel approach in terms of prevention of this potentially fatal complication when patients receive chemotherapy.