A Case of Parinaud Syndrome in a Patient with Parkinson's Disease: Causal Association or Co-incidental?

Background: Parinaud syndrome is a dorsal mid-brain syndrome characterized by upgaze paralysis, convergence retraction nystagmus, and pupillary light-near dissociation. Infarctions or hemorrhages involving the mid-brain are the most frequent causes in older adults. Objective: To report a novel case of a patient who presented with classical parkinsonian signs and Parinaud syndrome. Material and Methods: Patient data were obtained from medical records from the Department of General Medicine, Burdwan Medical College and Hospital, Burdwan, West Bengal, India. Results: A 62-year-old previously healthy man presented with motor and non-motor symptoms of Parkinson's disease (PD) for the past 6 years. The neurological examination revealed an asymmetric resting tremor of the upper limbs with rigidity, bradykinesia, hypophonia, hypomimia, decreased blinking, and micrographia. The neuro-ophthalmological examination showed Parinaud syndrome. He was treated with levodopa-carbidopa and trihexyphenidyl. After 6 months and 1 year of follow-up, his neurological condition was re-assessed; motor symptoms improved substantially, but Parinaud syndrome persisted. Conclusions: Parinaud syndrome can be a potential manifestation of PD. A detailed neuro-ophthamological examination should be carried out even in patients having a diagnosis of classic PD in whom eye-movement abnormalities are distinctly infrequent.

A case of limb shaking transient ischaemic attack due to internal carotid artery dissection: an unusual presentation of fibromuscular dysplasia.

BACKGROUND: Fibromuscular dysplasia (FMD) has a high prevalence of associated nontraumatic carotid artery dissection, which could further result in transient ischaemic attack (TIA) or stroke. Limb shaking TIA is an unusual form of TIA that is commonly discribed in elderly patients with atherosclerotic backgrounds, while there are limited data about it in patients with FMD. Furthermore, discussions of limb shaking TIA in nonelderly patients are scarce. CASE PRESENTATION: An Asian 47-year-old female presented with intermittent involuntary movement of the left upper limb accompanied by neck torsion. The episode stopped soon after changing to the supine position. On native source images of time-of-flight magnetic resonance angiography (TOF-MRA), the right internal carotid artery showed a "dual lumen sign" with an intimal flap. On contrast-enhanced magnetic resonance angiography and sagittal black-blood T1WI, an intravascular haematoma with irregular lumen stenosis was observed, which overall indicated right internal carotid artery dissection. Digital subtraction angiography showed the characteristic "string-of-beads" appearance in the left internal carotid artery, and the presence of this sign pointed to the diagnosis of FMD. The patient was finally diagnosed with limb shaking TIA due to internal carotid dissection with fibromuscular dysplasia. The patient was prescribed dual anti-platelet therapy. The limb shaking vanished soon after admission with no reoccurrence in the three-month follow-up. CONCLUSIONS: This case demonstrates that limb shaking TIA can present in patients with FMD. Limb shaking TIA in nonelderly patients can be caused by multiple diseases, and more detailed patient guidance is required in clinical practice.

The Role of Alpha-Synuclein Deposits in Parkinson's Disease: A Focus on the Human Retina.

Parkinson's disease (PD) is a neurodegenerative condition characterized by the progressive deterioration of dopaminergic neurons in the central and peripheral autonomous system and the intraneuronal cytoplasmic accumulation of misfolded α-synuclein. The clinical features are the classic triad of tremor, rigidity, and bradykinesia and a set of non-motor symptoms, including visual deficits. The latter seems to arise years before the onset of motor symptoms and reflects the course of brain disease. The retina, by virtue of its similarity to brain tissue, is an excellent site for the analysis of the known histopathological changes of PD that occur in the brain. Numerous studies conducted on animal and human models of PD have shown the presence of α-synuclein in retinal tissue. Spectral-domain optical coherence tomography (SD-OCT) could be a technique that enables the study of these retinal alterations in vivo. The objective of this review is to describe recent evidence on the accumulation of native or modified α-synuclein in the human retina of patients with PD and its effects on the retinal tissue evaluated through SD-OCT.

Pros and Cons of Ablation for Functional Neurosurgery in the Neurostimulation Age.

Should one recommend stereotactic ablation for Parkinson disease, tremor, dystonia, and obsessive compulsive disorder, in this era of DBS? The answer depends on several variables such as the symptoms to treat, the patient's preferences and expectations, the surgeons' competence and preference, the availability of financial means (by government health care, by private insurance), the geographical issues, and not least the current and dominating fashion at that particular time. Both ablation and stimulation can be either used alone or even combined (provided expertise in both of them) to treat various symptoms of movement and mind disorders.

Genetic screening of Filipinos suspected with familial Parkinson's disease: A pilot study.

INTRODUCTION: Although genetic factors are known to play a role in the pathogenesis of Parkinson's disease (PD), true prevalence of familial PD is unknown. We conducted this pilot study to identify genes implicated in familial Parkinson's disease among Filipinos. METHODS: Eighteen Filipino patients belonging to 11 families with personal and family history of PD underwent thorough evaluation by movement disorders specialists. Samples were analyzed in Juntendo University, Tokyo, Japan. Sanger sequencing of polymerase chain reaction products was performed. Each sample was screened for 23 genes (SNCA, PARK 2, UCHL1, PINK 1, DJ-1, LRRK2, ATP13A2, GIGYF2, HTRA2, PLA266, FBX07, VPS35, EIF461, DNAJC13, CHCHD2, GCH1, MAPT, NR4A2, VPS13c, PSEN1, and GRN). RESULTS: Out of 18 patients, six harbored Parkinson-related gene mutations. Five individuals from three families were positive for PINK1 c.10140T > C(p.L347P) mutation while one had heterozygous variant PRKN c.136G>T(p.A465) gene mutation. Three families displayed autosomal recessive pattern while one family with PINK1 mutation showed autosomal dominant mode of inheritance. Bradykinesia and tremor were predominant symptoms. Mean age at onset of symptoms was 40.4 years among those with PINK1 mutations. CONCLUSION: In this study, we presented the clinical profiles and identified two genetic mutations among a small group of Filipino patients with familial PD. They were congruent with most studies showing these mutations as the most common causes of autosomal recessive early-onset PD. Preliminary data from this pilot study will guide planning for larger scale studies, such as collaborative projects including The Global Parkinson's Genetics Program (GP2).

Improved Parkinsonian tremor quantification based on automatic label modification and SVM with RBF kernel.

Objective. The quantitative assessment of Parkinsonian tremor, e.g. (0, 1, 2, 3, 4) according to the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, is crucial for treating Parkinson's disease. However, the tremor amplitude constantly fluctuates due to environmental and psychological effects on the patient. In clinical practice, clinicians assess the tremor severity for a short duration, whereas manual tremor labeling relies on the clinician's physician experience. Therefore, automatic tremor quantification based on wearable inertial sensors and machine learning algorithms is affected by the manual labels of clinicians. In this study, an automatic modification method for the labels judged by clinicians is presented to improve Parkinsonian tremor quantitation.Approach. For the severe overlapping of dynamic feature range between different severities, an outlier modification algorithm (PCA-IQR) based on the combination of principal component analysis and interquartile range statistic rule is proposed to learn the blurred borders between different severity scores, thereby optimizing the labels. Afterward, according to the modified feature vectors, a support vector machine (SVM) with a radial basis function (RBF) kernel is proposed to classify the tremor severity. The classifier models of SVM with RBF kernel,k-nearest neighbors, and SVM with the linear kernel are compared.Main results. Experimental results show that the proposed method has high classification performance and excellent model generalization ability for tremor quantitation (accuracy: 97.93%, precision: 97.96%, sensitivity: 97.93%, F1-score: 97.94%).Significance. The proposed method may not only provide valuable assistance for clinicians to assess the tremor severity accurately, but also provides self-monitoring for patients at home and improve the assessment skills of clinicians.

Valproate-Associated Hyperammonemic Encephalopathy: Clinical Correlates and Management Strategies in a Tertiary Care Center.

BACKGROUND: Common adverse effects of valproate include sedation, tremor, gastrointestinal effects, and weight gain. Valproate-associated hyperammonemic encephalopathy (VHE) is an uncommon adverse effect of valproate therapy, which includes symptoms such as tremors, ataxia, seizures, confusion, sedation and coma. We report clinical features and management of 10 cases of VHE in a tertiary care center. METHODS: In a retrospective chart review of case records from January 2018 to June 2021, 10 patients with VHE were identified and included in this case series. The data collected include demographic information, psychiatric diagnosis, comorbidities, liver function tests, serum ammonia and serum valproate levels, dosages and duration of valproate, management of hyperammonemia including dosage variations, discontinuation, adjuvant drugs used, and whether rechallenge was done. RESULTS: The most common indication of starting valproate was bipolar disorder (n = 5). All the patients had more than one physical comorbidity and risk factors for developing hyperammonemia. Seven patients received valproate at a dose higher than 20 mg/kg. The duration of valproate use varied from 1 week to 19 years before developing VHE. Dose reduction or discontinuation and lactulose were the most common management strategies used. All 10 patients improved. Among the 7 patients in whom valproate was discontinued, for 2 patients valproate was reinitiated in inpatient care with careful monitoring and was found to be well tolerated. CONCLUSIONS: This case series highlights the need for a high index of suspicion for VHE as it is frequently associated with a delayed diagnosis and recovery in psychiatric settings. Screening for risk factors and serial monitoring may allow earlier diagnosis and management.

Between Order and Chaos: Understanding the Mechanism and Pathology of RAN Translation.

Repeat-associated non-AUG (RAN) translation is a pathogenic mechanism in which repetitive sequences are translated into aggregation-prone proteins from multiple reading frames, even without a canonical AUG start codon. Since its discovery in spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1), RAN translation is now known to occur in the context of 12 disease-linked repeat expansions. This review discusses recent advances in understanding the regulatory mechanisms controlling RAN translation and its contribution to the pathophysiology of repeat expansion diseases. We discuss the key findings in the context of Fragile X Tremor Ataxia Syndrome (FXTAS), a neurodegenerative disorder caused by a CGG repeat expansion in the 5' untranslated region of FMR1.

Reduced platelet 5-HT content is associated with rest tremor in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is highly heterogeneous in manifestations and pathogenesis. Serotonergic neurotransmitter system dysfunction is frequently implicated in PD tremor. Serotonin (5-HT) content in platelets is highly correlated with that in cerebrospinal fluid. In this study, we aimed to understand whether and how platelet 5-HT content reflects tremor in PD. METHOD: A total of 139 Chinese PD patients met with inclusion criteria were recruited. Motor and non-motor scores, and disease severity were evaluated. Patients were classified into subtypes of tremor-dominant (TD) and non-tremor-dominant (NTD). Peripheral platelets were isolated, and platelet 5-HT levels were measured. RESULTS: Platelet 5-HT content was lower in PD patients of TD subtype than in NTD subtype. Multifactor risk analysis showed that this lower content was independently associated with the TD phenotype. Platelet 5-HT level was inversely correlated with total tremor score, rest tremor amplitude score, rest tremor constancy score, and index of rest tremor, but not with postural tremor score, and kinetic tremor score. CONCLUSION: The cross-sectional study demonstrates that reduced platelet 5-HT content is associated with PD rest tremor. Our results support the involvement of serotonergic disturbance in PD rest tremor and indicate that 5-HT reduction can be manifested in peripheral platelets.

Progressive tremor and motor impairment in seizure-prone mutant tremor mice are associated with neurotransmitter dysfunction.

BACKGROUND: The tremor mutant mice present motor impairments comprised of whole-body tremors, ataxia, decreased exploratory behavior, and audiogenic seizures. OBJECTIVES: This study aims to investigate the development of motor dysfunction in this mutant mouse and the relationships with cortical, striatal, and cerebellar levels of GABA, glutamate, glycine, dopamine (DA), serotonin (5-HT), noradrenaline (NOR), and its metabolites. The serum cytokines levels, myelin content, and the astrocytic expression of the glial fibrillary acidic protein (GFAP) investigated the possible influence of inflammation in motor dysfunction. RESULTS: Relative to wild-type (WT) mice, the tremor mice presented: increased tremors and bradykinesia associated with postural instability, decreased range of motion, and difficulty in initiating voluntary movements directly proportional to age; reduced step length for right and left hindlimbs; reduced cortical GABA, glutamate and, aspartate levels, the DOPAC/DA and ratio and increased the NOR levels; in the striatum, the levels of glycine and aspartate were reduced while the HVA levels, the HVA/DA and 5HIAA/5-HT ratios increased; in the cerebellum the glycine, NOR and 5-HIAA levels increased. CONCLUSIONS: We suggest that the motor disturbances resulted mainly from the activation of the indirect striatal inhibitory pathway to the frontal cortex mediated by GABA, glutamate, and aspartate, reducing the dopaminergic activity at the prefrontal cortex, which was associated with the progressive tremor. The reduced striatal and increased cerebellar glycine levels could be partially responsible for the mutant tremor motor disturbances.

Cerebellar repetitive transcranial magnetic stimulation versus propranolol for essential tremor.

BACKGROUND: Propranolol, a nonselective beta-adrenergic blocker, has long been used as one of the standard treatments for essential tremor (ET). Repetitive transcranial magnetic stimulation (rTMS) has also been used for a long time as a substitution therapy for ET patients. OBJECTIVE: The main aim of this study was to evaluate the antitremor effect of 1-Hz (low-frequency) cerebellar rTMS and compare it to the use of propranolol in ET patients. METHODS: In this single-blinded, randomized, controlled pilot study, a total of 38 patients with ET were randomized into two groups. One group (n = 20) received 1200 pulses of 1-Hz rTMS at an intensity of 90% of the resting motor threshold to the bilateral cerebellar region for 10 days. Another group (n = 18) received oral propranolol for 30 days. The initial dose was 30 mg/day, which was increased to 60 mg/day after 5 days, then to 90 mg/day on the 11th day, and continued thereafter for 20 days. The Fahn-Tolosa-Marin (FTM) clinical scale was assessed at baseline and at days 5, 10, and 30 to evaluate tremor severity, specific motor tasks, and functional disability. RESULTS: Low-frequency rTMS of the cerebellum significantly improved tremor severity, specific motor tasks (writing, spiral drawing, and pouring), and FTM total scores on days 10 and 30. Nevertheless, we found no significant difference in functional disability at any point in time (p > .05). There were no statistically significant differences in FTM Part A, Part B, Part C scores and total scores of patients in propranolol group on days 5 and 10 compared with before treatment (p > .05). However, FTM total scores and FTM Part A, Part B, and Part C scores were significantly improved for patients when the dose of propranolol was 90 mg/day on day 30. Our study showed that there was no statistically significant difference in the total FTM scores and FTM Part A, Part B, and Part C scores between rTMS and propranolol on days 5, 10, and 30 (p > .05). CONCLUSION: We conclude that both cerebellar low-frequency rTMS and propranolol could be effective treatment options for patients with ET, but it is not clear which method is more effective.

Small amount of alcohol did not deteriorate microsurgical dexterity: a prospective laboratory study.

BACKGROUND: Alcohol consumption has been reported to deteriorate surgical performance both immediately after consumption as well as on the next day. We studied the early effects of alcohol consumption on microsurgical manual dexterity in a laboratory setting. METHOD: Six neurosurgeons or neurosurgical residents (all male) performed micro- and macro suturing tasks after consuming variable amounts of alcohol. Each participant drank 0-4 doses of alcohol (14 g ethanol). After a delay of 60-157 min, he performed a macrosurgical and microsurgical task (with a surgical microscope). The tasks consisted of cutting and re-attaching a circular latex flap (diameter: 50 mm macrosuturing, 4 mm microsuturing) with eight interrupted sutures (4-0 multifilament macrosutures, 9-0 monofilament microsutures). We measured the time required to complete the sutures, and the amplitude and the frequency of physiological tremor during the suturing. In addition, we used a four-point ordinal scale to rank the quality of the sutures for each task. Each participant repeated the tasks several times on separate days varying the pre-task alcohol consumption (including one sober task at the end of the data collection). RESULTS: A total of 93 surgical tasks (47 macrosurgical, 46 microsurgical) were performed. The fastest microsurgical suturing (median 11 min 49 s, [interquartile range (IQR) 654 to 761 s]) was recorded after three doses of alcohol (median blood alcohol level 0.32‰). The slowest microsurgical suturing (median 15 min 19 s, [IQR 666 to 1121 s]) was observed after one dose (median blood alcohol level 0‰). The quality of sutures was the worst (mean 0.70 [standard deviation (SD) 0.48] quality points lost) after three doses of alcohol and the best (mean 0.33 [SD 0.52] quality points lost) after four doses (median blood alcohol level 0.44‰). CONCLUSIONS: Consuming small amount of alcohol did not deteriorate microsurgical performance in our study. An observed reduction in physiological tremor may partially explain this.

MRgFUS thalamotomy for the treatment of tremor: evaluation of learning curve and operator's experience impact on the procedural and clinical outcome.

BACKGROUND: MRgFUS Vim ablation is increasingly used for the treatment of tremor in ET e PD patients but there is little published research on the importance of operator experience in this procedure. This study aims to evaluate the learning curve and the influence of the operator experience on the procedural and clinical outcomes. METHODS: We retrospectively evaluated 90 patients (38 ET, 52 PD) submitted to MRgFUS unilateral thalamotomy in the period between February 2018 and July 2020. Clinical endpoints, procedural times, and technical parameters were recorded in all procedures. Based on the time of treatment, patients were divided into three groups of 30 units each, comparing all variables between each time period group. RESULTS: In Group A, the average patient preparation time was 120.6 min, the treatment time was 105.2 min, the number of was sonications 14.1, and the mean target shifts 3.1. In Group B, the mean preparation time was 105.5 min, the treatment time was 89.5 min, the number of sonications was 13.2, and the target shifts 3.0. Group C showed inferior values of preparation time (101.9 min), treatment time (71.7 min), numbers of sonications (10.6), and shifts (1.7). Thalamotomy-related complications occurred in 9 patients of Group A, 2 of Group B, and 5 of Group C. Tremor relapse occurred in 7 patients of Group A, 3 of Group B, and 2 of Group C. The days of hospitalization were comparable in the three groups. CONCLUSIONS: The operators experience is associated with the improvement of clinical and procedural outcome in MRgFUS thalatomy for the treatment of ET and PD tremor.

Hyperkinetic movement disorders following SARS-CoV-2 infection and vaccination - an update.

The aim of this review was to summarise current knowledge regarding hyperkinetic movement disorders related to SARS-CoV-2 infection and vaccination in terms of phenomenology, epidemiology, pathogenesis and treatment. After a thorough review of the PubMed and Google Scholar databases (2020-2022), we identified myoclonus and ataxia sometimes accompanied by opsoclonus (AMS) as the two most frequent COVID-19 sequelae, with chorea, tremor and dystonia being very rare. The pathogenesis seems to be variable, but in the majority of AMS cases it was autoimmunological, with good response and recovery after corticosteroids or intravenous immunoglobulins infusions. Vaccination may be complicated by hyperkinetic movement disorders (e.g. tremor, dystonia), but this is very rare. Patients with Deep Brain Simulation depletion should not be postponed due to lockdowns as this may result in fatal outcomes.

Identification of Parkinson's disease-associated chromatin regulators.

Parkinson's disease (PD) is a common neurological disorder that causes quiescent tremors, motor delays, depression, and sleep disturbances. Existing treatments can only improve symptoms, not stop progression or cure the disease, but effective treatments can significantly improve patients' quality of life. There is growing evidence that chromatin regulatory proteins (CRs) are involved in a variety of biological processes, including inflammation, apoptosis, autophagy, and proliferation. But the relationship of chromatin regulators in Parkinson's disease has not been studied. Therefore, we aim to investigate the role of CRs in the pathogenesis of Parkinson's disease. We collected 870 chromatin regulatory factors from previous studies and downloaded data on patients with PD from the GEO database. 64 differentially expressed genes were screened, the interaction network was constructed and the key genes with the top 20 scores were calculated. Then we discussed its correlation with the immune function of PD. Finally, we screened potential drugs and miRNAs. Five genes related to the immune function of PD, BANF1, PCGF5, WDR5, RYBP and BRD2, were obtained by using the absolute value of correlation greater than 0.4. And the disease prediction model showed good predictive efficiency. We also screened 10 related drugs and 12 related miRNAs, which provided a reference for the treatment of PD. BANF1, PCGF5, WDR5, RYBP and BRD2 are related to the immune process of Parkinson's disease and can predict the occurrence of Parkinson's disease, which is expected to become a new target for the diagnosis and treatment of Parkinson's disease.

The Influence of Fatigue on the Characteristics of Physiological Tremor and Hoffmann Reflex in Young Men.

The aim of the study was to determine the relationship between changes in physiological tremor after exercise and changes in the traction properties of the stretch reflex indirectly assessed using the Hoffmann reflex test. The research involved 19 young men practicing canoe sprint (age 16.4 ± 0.7 years, body mass 74.4 ± 6.7 kg, body height 182.1 ± 4.3 cm, training experience 4.8 ± 1.6 years). During resting tests, Hoffmann reflex measurements were performed from the soleus muscle, physiological tremor of the lower limb, and the blood lactate concentration was determined. Then, a graded test was carried out on the kayak/canoe ergometer. Immediately after the exercise and in the 10th and 25th minute following the exercise, Hoffmann's reflex of the soleus muscle was measured. The physiological tremor was measured at 5, 15 and 30 min after exercise. Blood lactate concentrations were determined immediately after physiological tremor. Both the parameters of Hoffmann's reflex and physiological tremor changed significantly after exercise. There were no significant interrelationships between Hoffmann reflex measurements and physiological tremor in resting and post-exercise conditions. No significant correlation was detected between changes in physiological tremor and changes in Hoffmann reflex parameters. It is to be assumed that there is no connection between a stretch reflex and a physiological tremor.

Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in VPS13D-Related Disorder.

VPS13D is one of four human homologs of the vacuolar sorting protein 13 gene (VPS13). Biallelic pathogenic variants in the gene are associated with spastic ataxia or spastic paraplegia. Here, we report two patients with intronic pathogenic variants: one patient with early onset severe spastic ataxia and debilitating tremor, which is compound-heterozygous for a canonical (NM_018156.4: c.2237-1G > A) and a non-canonical (NM_018156.4: c.941+3G>A) splice site variant. The second patient carries the same non-canonical splice site variant in the homozygous state and is affected by late-onset spastic paraplegia. We confirmed altered splicing as a result of the intronic variants and demonstrated disturbed mitochondrial integrity. Notably, tremor in the first patient improved significantly by bilateral deep brain stimulation (DBS) in the ventralis intermedius (VIM) nucleus of the thalamus. We also conducted a literature review and summarized the phenotypical spectrum of reported VPS13D-related disorders. Our study underscores that looking for mutations outside the canonical splice sites is important not to miss a genetic diagnosis, especially in disorders with a highly heterogeneous presentation without specific red flags.

Botulinum Toxin Treatment of Motor Disorders in Parkinson Disease-A Systematic Review.

This review provides an up-to-date literature account on the efficacy of Botulinum toxin treatment for common motor disorders of Parkinson Disease. The reviewed disorders include the common motor disorders in PD such as tremor, focal foot dystonia, rigidity and freezing of gait (FOG). In the area of Parkinson tremor, two newly described evaluation/injection techniques (Yale method in USA and Western University method in Canada) offer efficacy with low incidence of hand and finger weakness as side effects. Blinded studies conducted on foot dystonia of PD indicate that botulinum toxin injections into toe flexors are efficacious in alleviating this form of dystonia. Small, blinded studies suggest improvement of Parkinson rigidity after botulinum toxin injection; proof of this claim, however, requires information from larger, blinded clinical trials. In FOG, the improvement reported in open label studies could not be substantiated in blinded investigations. However, there is room for further controlled studies that include the proximal lower limb muscles in the injection plan and/or use higher doses of the injected toxin for this indication.

Phenomenology and Physiology of Tacrolimus Induced Tremor.

Background: Tacrolimus is a potent immunosuppressant drug commonly used after solid organ transplant surgery. The use of this drug is frequently associated with the emergence of tremors. There is little information on the clinical and physiological characteristics of tacrolimus-induced tremors. Characterizing these tremors is essential as they can promote the development of specific therapies. Methods: We describe four patients placed on tacrolimus immunosuppressant therapy following kidney transplant surgery and who developed tremors impacting their daily functional activities. We describe the clinical and physiological characteristics of the tremor and the response generated after a limb cooling test. Results: A postural and kinetic tremor mainly involving the distal hands was observed in our cohort. In the accelerometer-based assessment, the tremor amplitude was noted to be mild to moderate, and the frequency was 5-6 Hz. Cooling the forearm and the hand led to a temporary albeit significant reduction of tremor amplitude (p = 0.03). Limb cooling lowered the tremor frequency by 1 Hz in two patients with no change in the other two patients, and the statistical comparison was not significant (p > 0.05). Conclusions: Limb cooling may be pursued as a therapeutic option for addressing tacrolimus-induced tremor, as the patients in our cohort benefitted from temporary tremor suppression.