Holmes Tremor Research Articles

Delayed presentation of hypertrophic olivary degeneration following pontine hemorrhage: Two case reports highlighting clinical presentation, diagnostics and multidisciplinary treatment

Hypertrophic Olivary Degeneration (HOD) is a rare degenerative disease that causes hypertrophy rather than atrophy. The classical presentation of HOD is palatal myoclonus but HOD may also present with tremor, and stiffness in the extremities. In this paper, case report 1 was a man aged 46 years with HOD and Holmes tremor spreading to the head, trunk and bilateral upper and lower extremities after pontine hemorrhage. In case report 2, a 50-year-old man with HOD displayed a sense of stiffness in his left upper and lower extremities after pontine hemorrhage. Although pontine hemorrhage may cause tremor and stiffness in the late period, the development of focused imaging promotes and improves HOD diagnosis. HOD related symptoms can be partially ameliorated by the described medication and rehabilitation regimen.

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.

Clinical Features, Neuroimaging, and Levodopa-Responsiveness in Holmes' Tremor: A Video-Based Case-Series with a Review of the Literature.

Holmes' tremor (HT) is a low-frequency tremor characterized by a combination of rest, posture, and action components. We are reporting the clinical features, neuroimaging findings, and levodopa responsiveness in 12 patients with HT. The majority of the patients were male (11/12). Dystonia was observed in 10 patients and the remaining two patients had head tremor, a "forme-fruste" of cervical dystonia. The underlying etiologies were vascular (n=8), head trauma (n=2), and tumor resection (n=2). Neuroimaging showed isolated involvement of the midbrain in four, thalamus in two, and basal ganglia and cerebellum in one patient each. A combination of the lesion (thalamus and cerebellum=2; cerebellopontine angle=1, and cortical/subcortical=1) was present in four patients. Levodopa responsiveness was seen in 75% of patients including one with levodopa-induced dyskinesia. Of 139 patients from 49 studies, levodopa was tried in 123 patients. Improvement with levodopa was seen in 71 patients (57.72%). No improvement with levodopa was observed in 33 patients (26.82%) and details regarding therapeutic response were unavailable in 19 patients (15.44%). Dystonia is an important clinical manifestation of HT. Levodopa responsiveness seen in the majority of the patients is consistent with the hypothesis that nigrostriatal pathway damage is crucial for the pathophysiology of HT.

Applicability of Botulinum Toxin in Treatment of Holmes Tremor: Our Cases and Detailed Review of Current Literature

Applicability of Botulinum Toxin in Treatment of Holmes Tremor: Our Cases and Detailed Review of Current Literature

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.

Effects of Deep Brain Stimulation on Lower Urinary Tract Function in Neurological Patients

BackgroundDeep brain stimulation (DBS) has clear beneficial effects on motor signs in movement disorders, but much less is known about its impact on lower urinary tract (LUT) function. ObjectiveTo evaluate the effects of DBS on LUT function in patients affected by movement disorders. Design, setting, and participantsWe prospectively enrolled 58 neurological patients affected by movement disorders, who were planned to receive DBS. InterventionDBS in the globus pallidus internus, ventral intermediate nucleus of the thalamus, or subthalamic nucleus. Outcome measurements and statistical analysisSubjective symptom questionnaires (International Prostate Symptom Score) and objective urodynamic studies were carried out before implantation of the DBS leads and several months after surgery. After DBS surgery, urodynamic investigations were performed with DBS ON as well as DBS OFF. Results and limitationsWe enrolled patients suffering from Parkinson’s disease (n = 39), dystonia (n = 11), essential tremor (n = 5), Holmes tremor (n = 2), and multiple sclerosis with tremor (n = 1). DBS of the globus pallidus internus resulted in worsening of LUT symptoms in 25% (four of 16) of the cases. DBS of the subthalamic nucleus in patients with Parkinson’s disease led to normalization of LUT function in almost 20% (six of 31 patients), while a deterioration was seen in only one (3%) patient. DBS of the ventral intermediate nucleus of the thalamus improved LUT function in two (18%) and deteriorated it in one (9%) patient with tremor. ConclusionsDBS effects on LUT varied with stimulation location, highly warranting patient counseling prior to DBS surgery. However, more well-designed, large-volume studies are needed to confirm our findings. Patient summaryIn this report, we looked at outcomes of deep brain stimulation on lower urinary tract function. We found that outcomes varied with stimulation location, concluding that counseling of patients about the effects on lower urinary tract function is highly recommended prior to surgery.

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.

Quantitative motion analysis and clinical characteristics of Holmes tremor as compared to other tremor types (S32.008)

Quantitative motion analysis and clinical characteristics of Holmes tremor as compared to other tremor types (S32.008)

Early Recurrence of Holmes Tremor after Radiofrequency Thalamotomy

Early Recurrence of Holmes Tremor after Radiofrequency Thalamotomy

Case report of holmes tremor and brief literature review

Introduction: Holmes Tremor is a slow frequency tremor, with an irregular presentation of rest and intention tremor, with postural component not obligatory. The Holmes tremor physiopathology, although not completely elucidated, can be explained by lesions in both basal ganglia-thalamo-cortical loop and cerebellum-thalamo cortical loop, and can be treated with a conservative approach– pharmacological treatment – or with surgery. It is reported a case that a surgery was elected as treatment, that resulted in a stimulation of the Ventralis Intermedius (Vim) and Zona Incerta (ZI). Case Presentation: Female patient, 41 years old, with Holmes Tremor involving both upper limbs, more predominant on the right side, and affecting more the proximal than the distal region of the limb. The tremor was both of rest and action, exacerbated by movement, anxiety, and stress. Due to functional impairment and failure of conservative neurological treatment with pharmacotherapy, a neurosurgical procedure was requested for implantation of two electrodes, targeting the Vim and ZI, on the left side for tremor control. Conclusion: Holmes Tremor is a complex syndrome and has its pathophysiology not so well elucidated. The case report describes an implantation of an electrode that had positive outcomes for the patient.

Electrophysiological testing aids the diagnosis of tremor and myoclonus in clinically challenging patients

ObjectiveWe investigated how clinical neurophysiological testing can help distinguish tremor and myoclonus and their subtypes. MethodsWe retrospectively analysed clinical and neurophysiological data from patients who had undergone polymyography (EMG + accelerometry) to diagnose suspected tremor or myoclonus. We show a systematic approach, which includes contraction pattern, rhythm regularity, burst duration and evidence of cortical drive. ResultsWe detected 773 patients in our database, of which 556 patients were ultimately diagnosed with tremor (enhanced physiological tremor n = 169, functional tremor n = 140, essential tremor n = 90, parkinsonism associated tremor n = 64, cerebellar tremor n = 19, Holmes tremor n = 12, dystonic tremor n = 8, tremor not further specified n = 9), 140 with myoclonus and 23 with a combination of tremor and myoclonus. Polymyography confirmed the presumptive diagnosis in the majority of the patients and led to a change of diagnosis in 287 patients (37%). Conversions between diagnoses of tremor and myoclonus occurred most frequently between enhanced physiological tremor, essential tremor, functional tremor and cortical myoclonus. ConclusionsNeurophysiology is a valuable additional tool in clinical practice to differentiate between tremor and myoclonus, and can guide towards a specific subtype. SignificanceWe show how the stepwise neurophysiological approach used at our medical center aids the diagnosis of tremor versus myoclonus.

The Temporal Course of the MRI Findings of Inferior Oliver Hypertrophy: The Clinicoradiologic Presentation of a Rare Patient with Holmes Tremor and Palatal Myoclonus.

The Temporal Course of the MRI Findings of Inferior Oliver Hypertrophy: The Clinicoradiologic Presentation of a Rare Patient with Holmes Tremor and Palatal Myoclonus.

Study on the pathogenesis of Holmes tremor by multimodal 3D medical imaging: case reports of three patients

BackgroundWe examined for the first time the imaging characteristics of Holmes tremor (HT) through multimodal 3D medical imaging.Case presentationThree patients with Holmes tremor who visited the Affiliated Hospital of Chengdu University of TCM from August 2018 to April 2021 were retrospectively investigated to summarize their clinical and imaging data.ResultsHolmes tremor in two of the three patients was caused by hypertensive cerebral hemorrhage and in the third patient induced by hemorrhage due to ruptured brain arteriovenous malformations. HT occurred 1 to 24 months after the primary disease onset and manifested as a tremor in the contralateral limb, mostly in the upper portion. Cranial MRI showed that the lesions involved the thalamus in all three patients. The damaged thalamic nuclei included the ventral anterior nucleus, ventral lateral nucleus and ventromedial lateral nucleus, and the damaged nerve fibers included left thalamocortical tracts in one patient. In the other two patients, the damaged thalamic nuclei included the centromedian and dorsomedial nucleus, and the damaged nerve fibers included left cerebellothalamic and thalamocortical tracts. One patient showed significant improvement after treatment with pramipexole while the other two patients exhibited a poor response, one of whom had no response to the treatment with pramipexole and was only significantly relieved by clonazepam.ConclusionWe used multimodal 3D medical imaging for the first time to analyze the pathogenesis of HT and found that multiple thalamic nuclei were damaged. The damaged nuclei and nerve fiber tracts of two patients were different from those of the third patient, with different clinical manifestations and therapeutic effects. Therefore, it is speculated that there may be multiple pathogeneses for HT.

Holmes tremor: a delayed complication after resection of brainstem cavernomas.

In this paper, the authors aimed to illustrate how Holmes tremor (HT) can occur as a delayed complication after brainstem cavernoma resection despite strict adherence to the safe entry zones (SEZs). After operating on 2 patients with brainstem cavernoma at the Great Metropolitan Hospital Niguarda in Milan and noticing a similar pathological pattern postoperatively, the authors asked 10 different neurosurgery centers around the world to identify similar cases, and a total of 20 were gathered from among 1274 cases of brainstem cavernomas. They evaluated the tremor, cavernoma location, surgical approach, and SEZ for every case. For the 2 cases at their center, they also performed electromyographic and accelerometric recordings of the tremor and evaluated the post-operative tractographic representation of the neuronal pathways involved in the tremorigenesis. After gathering data on all 1274 brainstem cavernomas, they performed a statistical analysis to determine if the location of the cavernoma is a potential predicting factor for the onset of HT. From the analysis of all 20 cases with HT, it emerged that this highly debilitating tremor can occur as a delayed complication in patients whose postoperative clinical course has been excellent and in whom surgical access has strictly adhered to the SEZs. Three of the patients were subsequently effectively treated with deep brain stimulation (DBS), which resulted in complete or almost complete tremor regression. From the statistical analysis of all 1274 brainstem cavernomas, it was determined that a cavernoma location in the midbrain was significantly associated with the onset of HT (p < 0.0005). Despite strict adherence to SEZs, the use of intraoperative neurophysiological monitoring, and the immediate success of a resective surgery, HT, a severe neurological disorder, can occur as a delayed complication after resection of brainstem cavernomas. A cavernoma location in the midbrain is a significant predictive factor for the onset of HT. Further anatomical and neurophysiological studies will be necessary to find clues to prevent this complication.

Erratum. Holmes tremor: a delayed complication after resection of brainstem cavernomas.

Erratum. Holmes tremor: a delayed complication after resection of brainstem cavernomas.

Motor-speech disorders in a patient with a vertebrobasilar stroke affected by coronavirus infection (clinical observation)

Amidst the growing coronavirus infection (COVID-19) pandemic, there is increasing evidence of the development of neurological complications of this disease and, especially, acute cerebrovascular accidents, and what is more, an increase in incidence rates of strokes is noted in the patients under the age of 50, who did not have risk factors for cerebrovascular diseases. The article examines several potential mechanisms that determine the relationships between ischemic stroke and COVID-19. A clinical case of the development of ischemic stroke in the vertebrobasilar system affected by the coronavirus infection is presented. The causal relationship between coronavirus infection and vascular catastrophe is discussed. In the described case, COVID-19 contributed to the decompensation of the patient’s associated risk factors. A feature of the described case is the delayed development of a rare motor disorder in the form of Holmes tremor and combined speech disorders (dysarthria and aftereffects of motor aphasia) in the patient. Holmes tremor is an unusual type of tremor characterized by a combination of rest, postural, and action tremors that predominantly affects the proximal limbs. This symptom is named after the British neurologist Gordon Holmes, who described a series of cases of an unusual variant of tremulous hyperkinesis in 1904. The article discusses the pathogenesis issues of the development of this condition and provides clinical criteria for Holmes tremor. This is a rather rare symptom, there are no data on large studies of this disorder in the literature, and it is mainly described in small series of clinical cases. The efficacy of Akatinol Memantine in the treatment of post-stroke speech disorders is discussed, and the rationale for prescribing this drug in the management of patients with post-stroke speech disorders is presented.

Multicenter Prospective Analysis of Hypertrophic Olivary Degeneration Following Infratentorial Stroke (HOD-IS): Evaluation of Disease Epidemiology, Clinical Presentation, and MR-Imaging Aspects

Introduction: Ischemic and hemorrhagic strokes in the brainstem and cerebellum with injury to the functional loop of the Guillain-Mollaret triangle (GMT) can trigger a series of events that result in secondary trans-synaptic neurodegeneration of the inferior olivary nucleus. In an unknown percentage of patients, this leads to a condition called hypertrophic olivary degeneration (HOD). Characteristic clinical symptoms of HOD progress slowly over months and consist of a rhythmic palatal tremor, vertical pendular nystagmus, and Holmes tremor of the upper limbs. Diffusion Tensor Imaging (DTI) with tractography is a promising method to identify functional pathway lesions along the cerebello-thalamo-cortical connectivity and to generate a deeper understanding of the HOD pathophysiology. The incidence of HOD development following stroke and the timeline of clinical symptoms have not yet been determined in prospective studies—a prerequisite for the surveillance of patients at risk.Methods and Analysis: Patients with ischemic and hemorrhagic strokes in the brainstem and cerebellum with a topo-anatomical relation to the GMT are recruited within certified stroke units of the Interdisciplinary Neurovascular Network of the Rhine-Main. Matching lesions are identified using a predefined MRI template. Eligible patients are prospectively followed up and present at 4 and 8 months after the index event. During study visits, a clinical neurological examination and brain MRI, including high-resolution T2-, proton-density-weighted imaging, and DTI tractography, are performed. Fiberoptic endoscopic evaluation of swallowing is optional if palatal tremor is encountered.Study Outcomes: The primary endpoint of this prospective clinical multicenter study is to determine the frequency of radiological HOD development in patients with a posterior fossa stroke affecting the GMT at 8 months after the index event. Secondary endpoints are identification of (1) the timeline and relevance of clinical symptoms, (2) lesion localizations more prone to HOD occurrence, and (3) the best MR-imaging regimen for HOD identification. Additionally, (4) DTI tractography data are used to analyze individual pathway lesions. The aim is to contribute to the epidemiological and pathophysiological understanding of HOD and hereby facilitate future research on therapeutic and prophylactic measures.Clinical Trial Registration: HOD-IS is a registered trial at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020549.

P-MD009. A neurophysiological characteristic of holme’s tremor with thalamic lesion

Introduction. Holme’s tremor (HT) is defined as a slow frequency tremor with irregular amplitude that mostly occurs at rest and worsens with voluntary movements. Dystonia can be occurred with HT and almost all patients had thalamic lesions. The neurophysiological characteristics of HT are limited. The objective of this case report is to highlight the neurophysiological finding of HT with co-occurrence of dystonia from the thalamic lesion. Results. We reported a 46-year-old female patient with 13-year-history of left cerebellar infarction with bilateral vertebral artery dissection post left cerebellar hemispherectomy with full recovery. Recently she presented with left hemiparesis, hemiataxia and left hemianesthesia, diagnosed as the right thalamic hemorrhage. Seven months later, she developed irregular jerky movement of the left hand as well as dystonic posture. The neurophysiological test was done to distinguish among HT, myorhythmia and dystonic tremor. The one-axis accelerometer (ACC) was put on the left thumb and surface EMG was placed on the abductor pollicis brevis (APB), the flexor digitorum superficialis of the left index (FDS 2) and the left extensor indicis proprius (EIP). The ACC and EMG data showed regular sinusoidal movement of left hand at the peak frequency of 3 Hz with synchronous contractions of the antagonist pairs at rest. The similar pattern with larger amplitude of movement was demonstrated during postural holding at several positions. These findings were consistent with the definition of HT with concomitant dystonia rather than myorhythmia or dystonic tremor. The functional imaging also revealed hypometabolism of right thalamus, cerebral peduncle, medulla and left cerebellum. Botulinum toxin injection was done with good benefit. Conclusion. The neurophysiological test is capable to differentiate HT from mimics. Sinusoidal rhythmic slow oscillation with co-contraction of the antagonist pairs at rest with worsening at voluntary movements might indicate HT with concomitant dystonia.

Symposium 2: Movement Disorders SY2.1. Evaluation of Tremor

Tremor is defined as an involuntary, rhythmic (regularly recurrent) and oscillatory (rotating around a central plane) movement of the body part. The evaluation of tremor should begin with careful history taking and a focused clinical examination on tremor phenomenology and associated neurological signs. The first step of the approach is to exclude tremor mimics such as myoclonus, clonus or other hyperkinetic movements. The second step is to carefully evaluate clinical features and establish whether the tremor is isolated or combined with other neurological problems and the predominant tremor is at rest or action. Tremor can be classified into syndromes depending on the characteristics (e.g. activation of tremor, distribution of tremor) and prominent additional signs. The common tremor syndromes during action are essential tremor, enhanced physiologic tremor, dystonic tremor, drug-induced tremor, cerebellar tremor, rubral tremor, and orthostatic tremor while the common tremor syndromes at rest are parkinsonian tremor. A detailed tremor history and neurological examination are usually enough for the clinical evaluation of tremor syndromes. However, the clinical presentations are sometimes complex and electrophysiologic investigations can be helpful in making the diagnosis of tremor subtypes. The basic neurophysiologic test is a multi-channel surface EMG combined with accelerometry to assess the distribution of tremor, tremor frequency, and amplitude during various types of activation of tremor, the effect of loading and distraction on tremor frequency and amplitude. The characteristics of central tremor syndromes are more stable tremor frequency and less influenced by loading compared to peripheral tremor syndromes. The peak tremor frequency can be overlapped among tremor subtypes but a unique tremor frequency can be found in some syndrome such as orthostatic tremor, cerebellar tremor and rubral tremor. The specific neurophysiologic procedures including distractibility and entrainment are sensitive and specific for functional tremors. Recently, more advanced neurophysiologic tests have emerged. There is a promising role of intermuscular coherence analysis in the differential diagnosis of tremor subtypes. Evaluation of tremor based on clinical and neurophysiological features are important, leading to the appropriate diagnosis and treatment.

Surgical Technique of Ventral Intermediate Thalamic Deep Brain Stimulation

Deep brain stimulation(DBS)of ventral intermediate(Vim)thalamic nucleus is an established procedure for tremor disorders, however, there are technical variations among specialists. The most common indications of Vim DBS are essential tremor(ET)and tremor dominant Parkinson's disease(PD), and less commonly other tremor disorders including Holmes tremor are treated with the same procedure. The variations of the surgical technique exist in the preoperative imagings and planning of the DBS electrode trajectory. In this review, we explain about the basic concept of Vim DBS and our surgical method.