Reversible encephalitis-like episodes in fragile X-associated tremor/ataxia syndrome: a case report.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by CGG repeat expansion of FMR1 gene. Both FXTAS and neuronal intranuclear inclusion disease (NIID) belong to polyglycine diseases and present similar clinical, radiological, and pathological features, making it difficult to distinguish these diseases. Reversible encephalitis-like attacks are often observed in NIID. It is unclear whether they are presented in FXTAS and can be used for differential diagnosis of NIID and FXTAS. CASE PRESENTATION: A 63-year-old Chinese male with late-onset gait disturbance, cognitive decline, and reversible attacks of fever, consciousness impairment, dizziness, vomiting, and urinary incontinence underwent neurological assessment and examinations, including laboratory tests, electroencephalogram test, imaging, skin biopsy, and genetic test. Brain MRI showed T2 hyperintensities in middle cerebellar peduncle and cerebrum, in addition to cerebellar atrophy and DWI hyperintensities along the corticomedullary junction. Lesions in the brainstem were observed. Skin biopsy showed p62-positive intranuclear inclusions. The possibilities of hypoglycemia, lactic acidosis, epileptic seizures, and cerebrovascular attacks were excluded. Genetic analysis revealed CGG repeat expansion in FMR1 gene, and the number of repeats was 111. The patient was finally diagnosed as FXTAS. He received supportive treatment as well as symptomatic treatment during hospitalization. His encephalitic symptoms were completely relieved within one week. CONCLUSIONS: This is a detailed report of a case of FXTAS with reversible encephalitis-like episodes. This report provides new information for the possible and rare features of FXTAS, highlighting that encephalitis-like episodes are common in polyglycine diseases and unable to be used for differential diagnosis.

Cerebrotendinous xanthomatosis with tremor as the main manifestation: A case report.

INTRODUCTION: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid metabolism disorder. It is caused by a defect in the sterol-27-hydroxylase gene, leading to the deposition of cholesteryl and bile alcohol in large amounts, causing a variety of clinical manifestations; however, tremor as the main manifestation of CTX has not been reported. PATIENTS CONCERNS AND CLINICAL FINDINGS: Herein, we report a 27-year-old woman, who developed head and body tremors at the age of 12 years. Many hospitals misdiagnosed her condition as idiopathic tremor and Parkinson disease, with a poor curative effect. PRIMARY DIAGNOSIS AND INTERVENTION: We diagnosed her with CTX and treated with chenodeoxycholic acid and clonazepam. CONCLUSION: The patient's condition considerably improved. This case could help avoid misdiagnosis and mistreatment in clinical practice.

[Tremor-dominant form of Parkinson's disease]. / Tremor-dominantnaya forma bolezni Parkinsona.

The article is of a review nature and is devoted to tremor, one of the maladaptive and difficult-to-treat symptoms of Parkinson's disease (PD). Along with the classic rest tremor, patients with PD may experience tremor of other modalities: postural tremor, kinetic tremor, which reflects a multimodal mechanism of tremor formation involving multiple neurotransmitter systems. The unpredictable response to therapeutic options, the ambiguous response to levodopa, also reflects the role of multiple underlying pathophysiological processes. Among the drug methods of tremor correction, preference is given to dopamine receptor agonists - due to the spectrum of their pharmaceutical action, high efficiency in relation to all leading motor and a number of non-motor manifestations. The evidence for advanced neurosurgical, non-invasive modalities is mixed, and there are insufficient comparative studies to assess their efficacy in patients with tremor-dominant forms of PD.

Analysis of gait characteristics and related factors in patients with Parkinson's disease based on wearable devices.

BACKGROUND: Postural instability and gait disorder dominant (PIGD) is one of the most common disabling symptoms of Parkinson's disease (PD), which seriously affects patients' quality of life. Therefore, it is essential to identify PIGD and develop targeted interventions to reduce the risk of PIGD in PD patients. AIM: This study aimed to investigate the gait characteristics of PD patients based on wearable devices and to establish a predictive model for their related influencing factors. METHODS: The retrospective medical records of patients from January 2020 to September 2023 were collected, including 159 patients with PD (divided into PIGD [n = 73] and non-PIGD [n = 86] groups) and 200 healthy patients (as the healthy control group). Information from social demographic data, a blood test, scale scores, gait analysis based on wearable devices, white matter lesions, and the Fazekas scale was extracted and analyzed. RESULTS: Compared with the healthy control group, the mean step length, mean rate, mean angular velocity, and step length were lower in the PD group, while the mean steps were higher in the turning test. The incidence of PIGD was 46% in PD patients, and PD patients with the non-tremor onset mode were more likely to develop PIGD than those with the tremor onset mode. Compared to the non-PIGD group, the PIGD group showed more serious gait problems in different experimental tasks and had a higher Hoehn and Yahr (H-Y) stage, Hamilton Anxiety Scale (HAMA) score, Hamilton Depression Scale score, periventricular white matter (PVWM) score, deep white matter score, and Fazekas scale score, but they had lower hemoglobin levels, D-dimer levels, Tinetti Balance scores, Tinetti Gait scores, Berg Balance Scale scores, and Mini-Mental State Examination (MMSE) scores. Logistic regression analysis showed that the MMSE score was negatively correlated with the occurrence of PIGD, while the HAMA score, H-Y stage, PVWM score, and non-tremor form of onset were positively correlated with the occurrence of PIGD CONCLUSION: The incidence of gait disorder in PD patients is higher than that in the normal population. Moreover, cognitive dysfunction, anxiety state, H-Y stage, PVWM score, and the non-tremor mode of onset can be considered independent risk factors for PIGD.

Flapping Tremor: Unraveling Asterixis-A Narrative Review.

Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed a narrative review to characterize further asterixis regarding nomenclature, historical aspects, etiology, pathophysiology, classification, diagnosis, and treatment. Asterixis has been classically used as a synonym for negative myoclonus across the literature and in previous articles. However, it is important to distinguish asterixis from other subtypes of negative myoclonus, for example, epileptic negative myoclonus, because management could change. Asterixis is not specific to any pathophysiological process, but it is more commonly reported in hepatic encephalopathy, renal and respiratory failure, cerebrovascular diseases, as well as associated with drugs that could potentially lead to hyperammonemia, such as valproic acid, carbamazepine, and phenytoin. Asterixis is usually asymptomatic and not spontaneously reported by patients. This highlights the importance of actively searching for this sign in the physical exam of encephalopathic patients because it could indicate an underlying toxic or metabolic cause. Asterixis is usually reversible upon treatment of the underlying cause.

Re-emergent Tremor in Parkinson's Disease: Evidence of Pathologic ß and Prokinetic γ Activity.

BACKGROUND: Re-emergent tremor is characterized as a continuation of resting tremor and is often highly therapy refractory. This study examines variations in brain activity and oscillatory responses between resting and re-emergent tremors in Parkinson's disease. METHODS: Forty patients with Parkinson's disease (25 males, mean age, 66.78 ± 5.03 years) and 40 age- and sex-matched healthy controls were included in the study. Electroencephalogram and electromyography signals were simultaneously recorded during resting and re-emergent tremors in levodopa on and off states for patients and mimicked by healthy controls. Brain activity was localized using the beamforming technique, and information flow between sources was estimated using effective connectivity. Cross-frequency coupling was used to assess neuronal oscillations between tremor frequency and canonical frequency oscillations. RESULTS: During levodopa on, differences in brain activity were observed in the premotor cortex and cerebellum in both the patient and control groups. However, Parkinson's disease patients also exhibited additional activity in the primary sensorimotor cortex. On withdrawal of levodopa, different source patterns were observed in the supplementary motor area and basal ganglia area. Additionally, levodopa was found to suppress the strength of connectivity (P < 0.001) between the identified sources and influence the tremor frequency-related coupling, leading to a decrease in ß (P < 0.001) and an increase in γ frequency coupling (P < 0.001). CONCLUSIONS: Distinct variations in cortical-subcortical brain activity are evident in tremor phenotypes. The primary sensorimotor cortex plays a crucial role in the generation of re-emergent tremor. Moreover, oscillatory neuronal responses in pathological ß and prokinetic γ activity are specific to tremor phenotypes. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Application of sensory nerve quantitative tests to analyze the subtypes of motor disorders in Parkinson's disease.

This study investigated the sensory nerve function in people with different subtypes of Parkinson's disease (PD), which included the tremor-dominant (TD) group (n = 30), postural instability and gait disorder (PIGD) group (n = 33), and healthy-controls (HC) group (n = 33). Sural nerve's current perception threshold (CPT) and pain tolerance threshold (PTT) in both feet were measured at different frequencies. Results were evaluated using the mini-mental state examination (MMSE), Hoehn Yahr scale (H-Y) , and 3-meter timed-up-and-go-test (TUGT). The MMSE scores of the TD and HC groups were higher than those of the PIGD group (TD < HC). The 3-meter TUGT scores of the PIGD group were higher than theTD and HC groups (TD > HC). The PIGD patients experienced a significantly shorter disease duration and higher H-Y score than the TD patients ( P  < 0.05). The values of 2 KHz CPT of left-side (CPTL), 2KHz CPT of right-side (CPTR), and 5 Hz CPTR in the PIGD group were significantly higher compared to the TD and HC groups ( P  < 0.05, Bonferroni correction). Additionally, the values of 250 Hz CPTL, 5 Hz CPTL, 250 Hz CPTR, 2 kHz PTT of left-side (PTTL), 250 Hz PTTL, and 5 Hz PTTL in the PIGD group were significantly elevated relative to the TD group ( P  < 0.05, Bonferroni correction). Distinctive current threshold perception and PTT of the sural nerve can be observed in patients with varying PD subtypes, and sensory nerve conduction threshold electrical diagnostic testing can detect these discrepancies in sensory nerve function.

Interdisciplinary insights into tremor in dystonia: Navigating clinical controversies, definitional challenges, and pathophysiological complexities.

This review delves into the historical evolution and ongoing controversy surrounding the relationship between tremor and dystonia. The Dystonia Consensus Panel and the International Parkinson's and Movement Disorders Society's Tremor Taskforce have attempted to define these entities, but the complexity arises when patients have a combination of both dystonia and tremor. The term "dystonic tremor" has sparked diverse interpretations, with debates over its clinical features and the need for more objectively defined characteristics. Logistic regression analyses in a large cohort of dystonia patients identified determinants such as body region affected by dystonia, dystonia severity, age, and recruitment site, with unexpected associations emphasizing the subjectivity in detecting and classifying tremor. The study further discovered diverse prevalence of "dystonic tremor" based on different definitions, revealing substantial variability among investigators. The recently convened Dystonia-Tremor panel aimed to address these challenges by proposing a more uniform nomenclature, emphasizing precise and descriptive terms. Despite the complexity, instrumented measures, such as electromyography, temporal discrimination threshold, blink reflex, and trajectory shape analysis, seem to be useful in distinguishing between tremor and dystonia. The pathophysiology debate centers around the involvement of the cerebello-thalamo-cortical and basal ganglia-thalamo-cortical circuits. Evidence supports the role of both circuits in driving the pathophysiology of dystonic tremor, challenging the notion of a clear dichotomy. The review concludes by emphasizing the need for a nuanced understanding, highlighting the intricate interplay between tremor and dystonia, and the potential of instrumental measures in advancing diagnostic accuracy.

Exploring obstructive sleep apnea and sleep architecture in Parkinson's disease motor subtypes.

INTRODUCTION: Parkinson's disease (PD) can be divided into motor subtypes: postural instability/gait difficulty (PIGD), tremor dominant, and indeterminate. This study aimed to assess differences in sleep structure and obstructive sleep apnea (OSA) between the PIGD and non-PIGD subtypes. METHODS: PD participants with or without OSA (defined as apnea-hypopnea index (AHI) ≥ 15 events/hour on overnight polysomnography) were included. Patients were separated into two groups: PIGD and non-PIGD. Linear regression was used to explore differences in sleep, AHI, and other respiratory parameters between groups (adjusted for variables determined a priori). Logistic regression adjusted for the same variables was used to determine if the proportion of patients with OSA differed across groups. Subset analyses were performed: subset 1 excluding patients on psychoactive medication; subset 2 excluding patients taking levodopa or dopaminergic agonists (DAs) at nighttime and subset 3 excluding patients on either of the abovementioned drugs. RESULTS: 146 participants were studied. The non-PIGD group had less N3 sleep compared to the PIGD group (12.4% vs 16.9% p = 0.06), reaching significance in subsets 1 and 3. The AHI was significantly lower in the PIGD group (p = 0.047), including when medication effects were removed (p < 0.05). OSA was more frequent in the non-PIGD group, but only significantly in subset 3 (adjusted OR 0.3, p = 0.04). CONCLUSION: OSA may be more severe in non-PIGD subtypes, and more frequent, in a subset free of psychoactive medication, and of levodopa and DAs, possibly owing to motor complications and dyskinesia. Future studies are required to confirm this.

[A case of Holmes tremor in which 123I-IMP SPECT and MRI findings suggest damage to the cerebellothalamic tract and the dentato-rubro-olivary pathway].

A 75-year-old woman was referred to our department in October 2022 with ataxia and involuntary movements of the right upper and lower limbs. She had experienced a left pontine hemorrhage in March 2021, which was managed conservatively. However, she had residual right-sided hemiplegia. In addition, she had cerebellar ataxia and a 2 |Hz resting tremor of the right upper and lower limbs, which was enhanced while maintaining posture and contemplation. Based on her history, and the findings of MRI and nuclear medicine imaging, we diagnosed the patient with Holmes tremor due to pontine hemorrhage. Holmes tremor is a rare movement disorder secondary to brainstem and thalamic lesions, characterized by a unilateral low-frequency tremor. In this case, 123I-IMP SPECT and MRI shows damage to the cerebellothalamic tract and dentaro-rubro-olivary pathway.

Resolution of Wing-Beating Tremor and Magnetic Resonance Imaging Lesions in Wilson's Disease Following Penicillamine.

Background: The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications. Phenomenology Shown: This video illustrates severe bilateral wing-beating tremor, moderate head and lower limb tremors, mild cervical dystonia, and subtle cerebellar ataxia, with nearly resolution after penicillamine treatment. Educational Value: This case highlights a typical aspect of WD, emphasizing the importance of early detection and treatment, and its correlation with MRI findings. Highlights: This case highlights the typical wing-beating tremor in Wilson's disease and its correlation with the involvement of the dentato-rubro-thalamic pathway. The early diagnosis and initiation of treatment with penicillamine resulted in an excellent clinical and radiological response.

Rhythmic Jaw Movements in Amyotrophic Lateral Sclerosis: Is It Clonus or Tremor?

Background: Jaw clonus refers to involuntary, rhythmic jaw contractions induced by a hyperactive trigeminal nerve stretch reflex; however, the movements, when triggered without a stretch, can be confused with a tremor. Phenomenology Shown: This video demonstrates a patient with amyotrophic lateral sclerosis presenting with rapid rhythmic jaw movements seen at rest, alongside a power spectrum analysis revealing a narrow high-frequency peak of 10 Hz. Educational Value: Rhythmic jaw movements are seen in many disorders such as Parkinson's disease, essential tremor, tardive syndromes, and cranial myorhythmias; however, a high-frequency movement, regardless of clonus or tremor, can indicate amyotrophic lateral sclerosis when accompanied by typical upper and lower motor neuron signs. Highlights: The presented video abstract shows a patient with amyotrophic lateral sclerosis with rhythmic jaw movements seen at rest. A power spectrum analysis of the rhythmic movements revealed a 10 Hz peak, a frequency higher than those seen in patients with Parkinson's disease, essential tremor, myorhythmia, and tardive syndromes.

Restless legs syndrome in the dominant Parkinson's side related to subthalamic deep-brain stimulation.

BACKGROUND: Restless legs syndrome (RLS) has an increased estimated prevalence in patients with Parkinson's disease (PS). RLS frequently mimics symptoms intrinsic to PD, such as motor restlessness, contributing to making its diagnosis challenging in this population. We report the case of a patient with new-onset RLS following subthalamic deep-brain stimulation (DBS-STN). We assessed symptoms using suggested immobilization test (SIT) with both DBS-STN activated and switched off. CASE DESCRIPTION: A 59-year-old man with idiopathic PD developed disabling RLS following DBS-STN at age 58, with PD onset at 50 manifesting as left arm tremor. Despite improved motor symptoms during the month following surgery, the patient experienced left leg discomfort at rest, transiently alleviated by movements due to an irrepressible urge to move, and worsened at night. Symptoms had no temporal relationship with oral dopa-therapy and disappeared when DBS-STN was deactivated. A 1 h SIT assessed motor behavior with irrepressible urge to move, as well as sensory symptoms by visual analog scale. After 30 m DBS-STN was switched off followed by the appearance of tremor in the left arm while both motor and sensory symptoms of RLS disappeared in the left leg. DISCUSSION: The mechanisms of DBS-STN's impact on RLS remain controversial. We hypothesize the DBS-STN to induce in our patient a hyperdopaminergic tone. DBS-induced and DBS-ameliorated RLS represent interesting conditions to further understand the pathophysiology of RLS. Moreover, the present observation suggests that SIT can be a valuable tool to assess RLS in PD patients before and after DBS-STN in future prospective studies.

A rare presentation of Wilson disease with neurological symptoms: Case report and genetic analysis.

RATIONALE: Wilson disease is a rare genetic disorder primarily associated with hepatic symptoms; however, its unique neurological presentation remains a subject of interest in the medical literature. This case report contributes to existing knowledge by highlighting the unusual manifestation of Wilson disease with significant neurological symptoms. PATIENT CONCERNS: The patient, pseudonym John Smith, presented with prominent neurological symptoms, including tremors, dystonia, and psychiatric manifestations. Clinical findings corroborated copper accumulation in the brain, prompting a thorough diagnostic investigation. DIAGNOSES: Genetic analysis revealed two ATP7B mutations, confirming the primary diagnosis of Wilson disease. This case underscores the importance of recognizing atypical neurological presentations in the context of this rare genetic disorder. INTERVENTIONS: Chelation therapy, initiated promptly upon diagnosis, targeted copper overload. The intervention led to notable improvements in neurological symptoms and psychiatric manifestations. The dosage and duration of treatment were adjusted based on regular monitoring. OUTCOMES: Regular follow-up revealed a positive trajectory, with reduced tremors and improved overall well-being. Genetic testing, coupled with clinical assessments, contributed to monitoring treatment efficacy and optimizing therapeutic interventions. LESSONS: The main takeaway lessons from this case include the significance of a comprehensive diagnostic approach, personalized therapeutic interventions, and the imperative to acknowledge the diverse clinical spectrum of Wilson disease. Early recognition and tailored treatment contribute to favorable outcomes in cases with atypical neurological presentations.

Roussy-Lévy Syndrome: Pes Cavus, Tendon Areflexia, Amyotrophy, Gait Ataxia, and Upper Limb Tremor in a Patient with CMT Neuropathy.

Background: Roussy-Lévy syndrome (RLS) is characterized by postural hand tremor seen in patients with familial autosomal dominant Charcot-Marie-Tooth (CMT) neuropathy. Phenomenology Shown: This video demonstrates irregular, jerky bilateral kinetic, postural, rest tremor affecting the right > left hand, along with pes cavus and gait ataxia in a patient with CMT disease. Educational Value: Pes cavus, tendon areflexia, sensory ataxia, and upper limb tremor should prompt consideration of CMT neuropathy. Highlights: This video abstract depicts a bilateral hand tremor characteristic of Roussy-Lévy syndrome seen in patients with Charcot-Marie-Tooth disease neuropathy. The significance of the abstract lies in the phenomenology and the physiology of the tremor seen in patients with genetically confirmed duplication of PMP22 gene.