EEG Findings in a Patient with Holmes Tremor after AVM Surgery: A Case Report and Literature Review.

Background: Holmes tremor (HT) is a rare motor disorder characterized by high-amplitude and low-frequency resting, intentional, and postural tremors. HT typically arises from disruptions in neural pathways, including the dopaminergic system. Its causes include cerebrovascular incidents, neoplasms, demyelination, and infections. Diagnosis involves thorough clinical, neurophysiological, and neuroimaging assessments. Our report details the clinical profile, neuroimaging and EEG results and levodopa treatment response of an HT patient after cerebral arteriovenous malformation (AVM) surgery. Case Report: A female patient who underwent AVM surgery developed head tremor and dystonia. Neuroimaging revealed left thalamus involvement. Video electroencephalography (EEG) revealed high-amplitude, low-frequency tremors. The patient responded well to levodopa treatment. Conclusions: Involuntary rhythmic or non-rhythmic movements are a primary clinical feature of HT. A differential diagnosis of epilepsy and HT can be achieved through neurophysiological monitoring, avoiding the overuse of antiepileptic drugs. Symptoms can be alleviated with levodopa intervention.

Vim-PSA Double-Target DBS for the Treatment of Holmes Tremor Secondary to Brainstem Hemorrhage: A Case Report.

We report the case of a 53-year-old man who was diagnosed with Holmes tremor and underwent deep brain stimulation of the ventro-intermediate thalamic nucleus and posterior subthalamic area. We assessed the patients' tremor with the Fahn-Tolosa-Marin Tremor Rating Scale at 1, 3, 6, 12 and 24 months after deep brain stimulation. Deep brain stimulation relieved the patient's tremor during the 24-month follow-up period.

Functional Neurological Disorders Among Patients With Tremor.

OBJECTIVE: Functional neurological disorders (FNDs) are increasingly recognized in the general population and neurology clinics, and there is evidence that patients with neurological disorders are more likely to have a FND. This study was designed to identify the clinical features of FNDs among patients with movement disorders when the two disorders coexist. METHODS: The clinical histories and video recordings of 150 consecutive patients with tremors were examined: the types of tremor included essential tremor; essential tremor plus; dystonic tremor; tremor associated with dystonia; and drug-induced, myoclonic, orthostatic, task-specific, parkinsonian, Holmes, and unclassified tremor. Using criteria for "possible" and "probable" coexistent FND, clinical features that helped differentiate between functional and other neurological tremors were identified. RESULTS: There were 27 (18%) patients with functional manifestations, and 17 (11% of full sample) of these patients had signs suggestive of comorbid functional tremor. Patients with comorbid functional manifestations were younger at presentation, and these patients had greater severity of tremor, particularly upper limb postural tremor. Functional manifestations were not more commonly observed among patients with any particular type of tremor, except for patients with Holmes tremor, who were more likely to have comorbid functional neurological manifestations. CONCLUSIONS: About 18% of patients with diverse types of tremors also had comorbid functional neurological manifestations. Of the coexistent FNDs, functional tremor was the most common. Patients with co-occurring functional and other neurological tremors presented for evaluation at a younger age and had greater severity of arm tremor than those without comorbid functional neurological manifestations.

Brainstem cavernous hemangioma with improvement of Holmes tremor on excision.

An 8-year-old boy presenting with left-angle paralysis, tremor in upper and lower extremities, and diplopia was diagnosed with hemorrhage from a mesencephalic cavernous hemangioma. He underwent hemangiomectomy through the occipital transtentorial approach 4 weeks post-hemorrhage, after which Holmes tremor (HT) markedly reduced. A year later, hemangioma has not recurred; he is now independent in his daily activities. Early intervention in the subacute stage allows for the complete removal of brainstem cavernomas (BSCs), with minimal risk of complications or sequelae. Proper timing and surgical approach for BSCs can prevent re-bleeding and improve HT after an initial hemorrhage, without any lasting negative consequences.

[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.

Analysis of Semiology, Lesion Topography and Treatment Outcomes: A Prospective Study on Post Thalamic Stroke Holmes Tremor.

OBJECTIVE: Holmes tremor (HT) comprises rest, postural and intention tremor subtypes, usually involving both proximal and distal musculature. Perturbations of nigro-striatal pathways might be fundamental in the pathogenesis of HT along with cerebello-thalamic connections. METHODS: Nine patients with an HT phenotype secondary to thalamic stroke were included. Epidemiological and clinical records were obtained. Structural and functional brain imaging were performed with magnetic resonance imaging (MRI) or computed tomography (CT) and positron emission tomography (PET), respectively. Levodopa was administered in sequentially increasing dosage, with various other drugs in case of inadequate response. Longitudinal follow-up was performed for at least three months. The essential tremor rating assessment scale (TETRAS) was used for assessment. RESULTS: The mean latency from stroke to tremor onset was 50.4 ± 30.60 days (range 21-90 days). Dystonia was the most frequently associated hyperkinetic movement (88.8%). Tremor was bilateral in 22.2% of participants. Clinical response was judged based on a reduction in the TETRAS score by a prefixed value (≥ 30%), pertaining to which 55.5% (n = 5) of subjects were classified as responders and the rest as non-responders. The responders showed improvement with significantly lower doses of levodopa than the remaining nonresponders (240 ± 54.7 mg vs. 400 ± 40.8 mg; p = 0.012). CONCLUSION: Although levodopa is useful in HT, augmenting the dosage of levodopa beyond a certain point might not benefit patients clinically. Topography of vascular lesions within the thalamus might additionally influence the phenomenology of HT.

The Relevance of Intraoperative Clinical and Accelerometric Measurements for Thalamotomy Outcome.

Thalamotomy alleviates medication-refractory tremors in patients with movement disorders such as Parkinson's Disease (PD), Essential tremor (ET), and Holmes tremor (HT). However, limited data are available on tremor intensity during different thalamotomy stages. Also, the predictive value of the intraoperative tremor status for treatment outcomes remains unclear. Therefore, we aimed to quantify tremor status during thalamotomy and postoperatively. Data were gathered between January 2020 and June 2023 during consecutive unilateral thalamotomy procedures in patients with PD (n = 13), ET (n = 8), and HT (n = 3). MDS-UPDRS scores and tri-axial accelerometry data were obtained during rest, postural, and intention tremor tests. Measurements were performed intraoperatively (1) before lesioning-probe insertion, (2) directly after lesioning-probe insertion, (3) during coagulation, (4) directly after coagulation, and (5) 4-6 months post-surgery. Accelerometric data were recorded continuously during the coagulation process. Outcome measures included MDS-UPDRS tremor scores and accelerometric parameters (peak frequency, tremor amplitude, and area under the curve of power (AUCP)). Tremor intensity was assessed for the insertion effect (1-2), during coagulation (3), post-coagulation effect (1-4), and postoperative effect (1-5). Following insertion and coagulation, tremor intensity improved significantly compared to baseline (p < 0.001). The insertion effect clearly correlated with the postoperative effect (ρ = 0.863, p < 0.001). Both tremor amplitude and AUCP declined gradually during coagulation. Peak frequency did not change significantly intraoperatively. In conclusion, the study data show that both the intraoperative insertion effect and the post-coagulation effect are good predictors for thalamotomy outcomes.

Giant Tumefactive Perivascular Spaces: An Unusual Cause of Holmes Tremor.

A 34-year-old man presented with a 2-year history of medically refractory Holmes tremor in the right upper limb. Magnetic resonance imaging revealed a large, nonenhancing, multiseptate cystic lesion of cerebrospinal fluid intensity in the left thalamopeduncular region causing brainstem compression and hydrocephalus. A diagnosis of giant tumefactive perivascular spaces was made after a biopsy ruled out an infectious or neoplastic etiology. Significant clinicoradiologic improvement was noted following a ventriculoperitoneal shunt. Giant tumefactive perivascular spaces should be included as one of the rare differentials of a large, nonenhancing cystic lesion situated along the course of perforator vessels. Treatment options include cerebrospinal fluid diversion with or without cyst fenestration.

Long-standing myoclonic hand tremor as an isolated symptom of hypertrophic olivary degeneration.

Hypertrophic olivary degeneration (HOD) is a rare condition caused by lesions of the dentato-rubro-olivary pathway, usually bilateral. We presented a case of a 64-year old male with HOD caused by a unilateral, posterior pontine cavernoma. The patient has not developed the typical palate myoclonus until recently. Isolated hand myoclonus with coexisting asterixis was present for years. This case shows unique HOD symptomatology and emphasizes the important role of MRI in the differential diagnosis of monomelic myoclonus.

Deep brain stimulation in posterior subthalamic area for Holmes tremor: Case reports with review of the literature.

Background: Holmes tremor (HT) is a refractory tremor associated with cortico-basal ganglia loops and cerebellothalamic tract abnormalities. Various drug treatments have been attempted; however, no treatment method has yet been established. Historically, thalamic deep brain stimulation (DBS) has been performed in medically refractory cases. Recently, the posterior subthalamic area (PSA) has been used for HT. Here, we report cases of HT and review the effectiveness and safety of PSA-DBS for HT. Cases: We conducted a retrospective chart review of two patients with HT who underwent PSA-DBS. Improvement in tremors was observed 1 year after surgery without apparent complications. Literature review: We identified 12 patients who underwent PSA-DBS for HT, including our cases. In six patients, PSA was targeted alone; for the rest, the ventralis intermediate nucleus (Vim) of the thalamus and PSA were simultaneously targeted. The Fahn-Tolosa-Marin Tremor Rating Scale improvement rates were 56.8% (range, 33.9-82.1%; n = 6) and 77.8% (range, 42.6-100%; n = 5) for the PSA-DBS and PSA+Vim-DBS, respectively. Conclusion: Reasonable improvements in HT were observed after PSA-DBS. PSA might be an appropriate target for improving the symptoms of HT. Long-term observations, accumulation of cases, and randomized studies are required in future.

Case report: Radiofrequency thalamotomy as palliative care for Holmes tremor in a patient with terminal cancer and cardiac pacemaker.

Background: Herein, we present a case report of a patient with Holmes tremor due to thalamic infarction with end-stage pancreatic cancer who underwent successful computed tomography (CT)-guided ventralis intermedius nucleus (Vim) thalamotomy as palliative care. Case Description: A 78-year-old man with gradually worsening involuntary movements on the left side of his body 2 years after a right thalamic infarction was referred to our institute. He had a history of chronic atrial fibrillation for which he was implanted with a cardiac pacemaker not compatible with magnetic resonance imaging. He also received adjuvant therapy for pancreatic cancer. As the involuntary movements interfered with his daily life, the patient elected for neurosurgical treatment despite having terminal cancer. Although the prognosis for pancreatic cancer was considered to be more than 6 months at the time of surgery, we performed CT-guided Vim thalamotomy under local anesthesia without pulse generator implantation considering the patient's general condition. The involuntary movements of the left side of the body reduced following surgery, thus improving his quality of life (QOL). However, 6 months after thalamotomy, the patient died of pancreatic cancer. Conclusion: Thalamotomy significantly reduced the involuntary movements immediately after the procedure. Therefore, thalamotomy can be performed under local anesthesia without the use of any device and may contribute to the improvement of QOL in terminal patients.

Deep brain stimulation of the posterior subthalamic area as an alternative strategy for management of Holmes tremor: A case report and review of the literature.

Background: Holmes tremor is often refractory to medical treatment and deep brain stimulation of the ventralis intermedius nucleus of the thalamus (VIM-DBS) is the intervention of choice in controlling the tremor. Herein, we present a beneficial alternative strategy for the management of such situations, considering the posterior subthalamic area (PSA) as the target of stimulation. Case Description: We report a 57-year-old male with the right-sided tremor following a traumatic brain injury 20 years ago. He had been diagnosed with Holmes tremor that was not responsive to nonsurgical therapeutic options. When refractoriness confirmed, he became a candidate for VIM-DBS. During the operation, by performing macrostimulation with a maximum of 2 mA of amplitude, the tremor had no response to the stimulation of different tracts, and severe right hemi-body paresthesia occurred; therefore, we modified our approach and targeted the PSA, which resulted in satisfactory control of the tremor. The permanent lead was implanted into the left side PSA. At 1-year follow-up, the right side tremor was under complete control. Conclusion: Our case and other similar pieces of evidence are consistently indicating the potential regulatory effects of PSA-DBS in controlling the Holmes tremor as a feasible alternative strategy when VIM-DBS does not provide a satisfactory response. However, further studies with larger sample size are required to evaluate the long-term response and its possible long-term stimulation-related effects.

Holmes tremor: an updated review.

Holmes tremor is a rare movement disorder with rest, intention and postural components, characterized by high amplitude and low frequency. It occurs mainly as a result of impairment of dopaminergic nigrostriatal system and cerebellothalamocortical or dentato-rubro-olivary pathways. The aetiologies of this tremor vary widely, including cerebrovascular events, tumours, demyelination and infections. Diagnosis is based on clinical examination, neurophysiological and neuroimaging studies. Magnetic resonance imaging (MRI) scan of the brain is the gold standard method for revealing the location and potential cause of the lesion, whereas dopamine transporter single photon emission with the use of 123I-FP CIT is useful in assessing the functional integrity of the nigrostriatal pathway. Although various treatment options are available, including pharmacological agents, deep brain stimulation and regional surgical techniques, its treatment remains challenging. Our deeper understanding of the disruption of associated neural brain circuits combined with recent genetic and molecular evidence will drastically improve its clinical evaluation and management.

An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor.

Deep brain stimulation (DBS) is part of state-of-the-art treatment for medically refractory Parkinson's disease, essential tremor or primary dystonia. However, there are multiple movement disorders that present after a static brain lesion and that are frequently refractory to medical treatment. Using Holmes tremor (HT) as an example, we discuss the effectiveness of currently available treatments and, performing simulations using a Markov Chain approach, propose that DBS with iterative parameter optimization is expected to be more effective than an approach based on sequential trials of pharmacological agents. Since, in DBS studies for HT, the thalamus is a frequently chosen target, using data from previous studies of lesion connectivity mapping in HT, we compared the connectivity of thalamic and non-thalamic targets with a proxy of the HT network, and found a significantly higher connectivity of thalamic DBS targets in HT. The understanding of brain networks provided by analysis of functional connectivity may thus provide an informed framework for proper surgical targeting of individual patients. Based on these findings, we argue that there is an ethical imperative to at least consider surgical options in patients with uncommon movement disorders, while simultaneously providing consistent information regarding the expected effectiveness and risks, even in a scenario of surgical-risk aversion. An approach based on n-of-1 DBS trials may ultimately significantly improve outcomes while informing on optimal therapeutic targets and parameter settings for HT and other disabling and rare movement disorders.

Evolving Concepts in Our Understanding and Treatment of Holmes Tremor, Over 100 Years in the Making.

Holmes Tremor (HT) is an irregular, slow-frequency (<4.5 Hz) tremor characterized by a combination of resting, postural, and action tremors mostly of the upper extremities. Symptoms of HT typically emerge 4 weeks to 2 years after a brain injury caused by a spectrum of etiologies. HT pathophysiology is thought to result from aberrant collateral axonal sprouting and synaptic dysfunction following neuronal damage. To date, the dopaminergic nigrostriatal system, cerebello-thalamo-cortical pathway, and dentate-rubro-olivary pathway have all been implicated in the clinical manifestations of HT. The diversity of HT etiologies usually requires a personalized treatment plan. Current treatment options include carbidopa-levodopa, levetiracetam, and trihexyphenidyl, and surgical management such as deep brain stimulation in selected medication-refractory patients. In this review we discuss the pathophysiology, etiology, neuroimaging, and the latest clinical guidelines for care and management of HT.

Wernekinck Commissure Syndrome with Holmes Tremor: A Report of Two Cases and Review of Literature.

Wernekinck commissure syndrome is a rare midbrain infarction, it consists of several symptoms including bilateral cerebellar ataxia, ophthalmoplegia, and palatal tremor. Holmes tremor is a rare clinical syndrome characterized by a combination of resting, postural, and action tremors. We describe two cases of Wernekinck commissure syndrome with Holmes tremor. To the best of our knowledge, it has been rarely reported in the literature to date. Both of the cases were presented with acute onset of bilateral cerebellar ataxia, dysarthria, and Holmes tremor. In the treatment, one patient was given "clonazepam and benheisol," the other was received acupuncture therapy, both of them showed a marked improvement in ataxia and tremor.