Figure 1
Neuroimaging advances in Holmes Tremor. Emerging multi-modal imaging strategies are increasingly being utilized to understand the underlying pathologic network in Holmes Tremor. These methods include functional MRI based functional connectivity, diffusion MRI based structural connectivity, and nuclear medicine imaging based neuronal connectivity.
Table 1
DBS outcomes for patients with HT in the literature.
| AUTHORS | PATIENTS AND ETIOLOGIES | DBS TARGETS | OUTCOMES | FOLLOW-UPS |
|---|---|---|---|---|
| Bargiotas et al. (2021) | Four patients (cerebellar stroke, stroke of the left lateral thalamus and the internal capsule, mesencephalic hemorrhage due to a cavernous malformation, or pontomesencephalic/thalamic strokes) | VIM or DRTT | 34–61% improvement in total TRS. Tremor improvement was lost in three years in three patients but sustained up to nine years in one patient. | Mean length of followup: 5 years |
| Cenzato et al. (2021) | Three patients who underwent resection of brainstem cavernomas | VIM for one patient, not described for two patients | Complete or almost complete tremor regression in all cases | N/A |
| Parker et al. (2021) | Hematoma in the right midbrain and cerebral peduncle | Left VIM + GPi | TRS 70% reduction in tremor | 10 years |
| Ghanchi et al. (2020) | Immune reconstitution inflammatory syndrome due to highlyactive antiretroviral therapy for HIV infection (symptoms for 6 months) | Left VIM | Significant tremor improvement in the right arm | 6 months |
| Razmkon et al. (2020) | Posttraumatic HT (symptoms for 6 years) | Right VIM | The patient experienced complete tremor suppression after DBS but developed localized infection. A rescue lesion through the implanted lead before explanting the DBS system controlled tremor well | 3 years |
| O’Shea et al. (2020) | Right medial cerebral peduncle and bilateral thalamic strokes (symptoms for 2 years) | Right Vim + Zi | Clear improvement in tremors bilaterally | N/A |
| Dec-wiek et al. (2019) | Three patients (one with multiple sclerosis and two with ischemic stroke) (symptoms for 1–39 years) | PSA | TRS 56% reduction in tremor | 1 year |
| Morishita et al. (2019) | Two patients (one with stroke and one with severe head trauma) (symptoms for 3 years) | VIM | TRS motor 52% reduction | 6 months |
| Yuk et al. (2019) | Brainstem hemorrhage (symptoms for 3 months) | Left VIM | TRS part A 75% reduction | 3 years |
| Martinez et al. (2018) | HIV-related vasculopathy associated with toxoplasmosis | Right Raprl | Robust and stable improvement in tremor | 2 years |
| Aydın et al. (2017) | Posttraumatic HT | Left VIM + GPi | TRS > 80% tremor improvement | 6 months |
| Toda et al. (2017) | Posttraumatic HT | VO + subthalamic region | While individual stimulation of each target was ineffective, an interleaved dual stimulation of both targets was effective | 6 years |
| Ramirez-Zamora et al. (2016) | Pontine and midbrain hemorrhage secondary to rupture of arteriovenous fistula (symptoms for 7 years) | Left GPi | 80% improvement in TRS right hand score | 6 months |
| Kilbane et al. (2015) [17] | 1. Right brainstem hemorrhage due to cavernous malformation 2.Multicystic brainstem tegmentum lesions 3.Left thalamic midbrain bullet fragment 4.Right thalamic/subthalamic infarction | Patient 1 had VIM/VOA and Gpi leads. Patient 2 and 4 had unilateral Gpi. Patient 3 had VIM/Gpi | TRS improved from a mean 53.25 points prior to surgery to 11.25% representing a 78.87% benefit | Mean length of followup: 33.7 months. |
| Espinoza-Martinez et al. (2015) [41] | Two patients with ICH due to cavernous malformations, four patients with cerebral infarction, two patients with ICH, and two patients with MS | Six with unilateral Gpi, one with bilateral Gpi, one with bilateral VIM, and two with unilateral VIM | 64% mean modified TRS improvement | Mean length of followup: 5.8 years |
| Follett et al. (2014) [38] | Posttraumatic HT (symptoms for 15 years) | Bilateral VIM | Reduction of tremor from a score of 3 to a score of 1 in the right arm and from 3.5 to 0 in the left arm (TETRAS scale) | 12 months |
| Grabska et al. (2014) [39] | Ischemic left thalamic stroke (symptoms 30 years) | Contralateral VOA and Zi | TRS 73% reduction in tremor | 4 years |
| Kobayashi et al. (2014) [40] | 1. Brainstem thalamus hemorrhage (symptoms for 6 years) 2. Cerebral infarction (symptoms for 3 years) 3. Intracerebral midbrain hemorrhage (symptoms 8 months) 4. Posttraumatic (symptoms for 2 years) | Four patients with dual-lead stimulation of ventralis oralis/ventralis intermedius nuclei (VO/VIM) and PSA | 87% mean improvement in tremor | 25 months |
| Castrop et al. (2013) [36] | 1.Hypertensive mesencephalic hemorrhage (symptoms for 1 year) 2.pontomesencephalic AVM hemorrhage (symptoms for 2 years) | Contralateral VIM | Good tremor suppression, whereas the other symptoms remained unchanged | 7 years and 6 years, respectively |
| Issar et al. (2013) [37] | One patient with posttraumatic tremor (symptoms for 6 months) with associated dystonia and cerebellar and cognitive difficulties. | Bilateral VIM | Partial benefit (CGI scale 3). No TRS available. Dystonia persisted | N/A |
| Aydin et al. (2013) | Midbrain and pons bleeded cavernoma | Right VIM + GPi | 68% improvement in TRS left hand score | 6 months |
| Acar et al. (2010) [35] | Subarachnoid hemorrhage (symptoms less than 1 month) | Bilateral VIM | No tremor and reduction in disability due to tremor | 3 months |
| Sanborn et al. (2009) | Midbrain cystic degeneration | Right VIM | Full tremor suppression | 2 years |
| Bandt et al. (2008) [31] | Left midbrain cerebral infarction (symptoms for 7 months) | Left lenticular fasciculus | Almost complete resolution of postural and intention tremors; scored 1/4 on the WHIGET | 16 months |
| Diederich et al. (2008) [32] | 1. L venous pontine angioma (symptoms for 7 years) 2. R midbrain hemiatrophy (symptoms for 32 years) | Contralateral VIM | Substantially ameliorated postural > rest > intention component | 7 years and 5 years, respectively |
| Peker et al. (2008) [33] | Left thalamic abscess (symptoms 18 months) | Right VIM | 90% overall improvement | 2.5 years |
| Plaha et al. (2008) [34] | No obvious MRI abnormality (symptoms for 6 years) | Contralateral caudal Zi | 70.2% improvement in total TRS | N/A |
| Lim et al. (2007) | Midbrain hemorrhage from a cavernous malformation (symptoms for 9 months) | Right VIM + VOA + GPi | 7% improvement with GPi DBS and 0% with VIM or VOA DBS | 8 months |
| Foote et al. (2006) [2] | Posttraumatic tremors: Three patients with symptoms for 16 years, 3 years, and 4 years | Two patients with VIM (border VIM/VOP and one with border VOA/VOP) | Total TRS improvement of 38.46 %, 48.33%, and 66.67 %, respectively | 12 months, 6 months, and 8 months, respectively |
| Nikkhah et al. (2004) [29] | 1.Right infarct midbrain (tremor symptoms 6 months); 2. Left thalamic AVM | Two patients with contralateral VIM | Almost complete tremor resolution (80% improvement). Dystonia and rigidity benefit reported | 7 months and 6 months, respectively |
| Piette et al. (2004) [30] | Pontine tegmental hemorrhage | Right VIM | Major functional improvement | 16 months |
| Romanelli et al. (2003) [27] | Unknown, severe symptoms 6 years | Left VIM and left STN | Tremor component improved 66%. | 2 years |
| Samadani et al. (2003) [28] | Left midbrain cavernous malformation (symptoms for 4 years) | Contralateral VIM | 57% increase in dexterity and four-point decrease in functional disability in TRS. | N/A |
| Pahwa et al. (2002) [26] | Midbrain cavernous hemangioma (symptoms for 3 years) | Right VIM | Significant improvement in postural and resting tremor; kinetic component persisted. | 10 months |
[i] AVM = arteriovenous malformation, DBS = deep brain stimulation, DRTT = dentatorubrothalamic tract, GPi = globus pallidus, HT = Holmes tremor, NA= not assessed, TRS = Fahn–Tolosa–Marin tremor rating scale, Raprl = prelemniscal radiation, VIM = ventral intermediate nucleus, VOA = ventral oral anterior nucleus, VOP = ventral oral posterior nucleus, Zi = zona incerta.
Video 1
Holmes tremor treated with unilateral Globus Pallidus Interna DBS. Patient is a 24-year-old male who suffered a pontine and midbrain hemorrhage secondary to rupture of AV fistula at age 17. In addition, a large varix was found in the vein of the Galen and brainstem in the setting of a complex AV fistula (Figure 2). Associated neurological symptoms include ataxia, oculomotor difficulties, spastic dysarthria, dystonia and right arm clumsiness. Over the following 6 months, the patient noted insidious onset of progressive right arm low-frequency resting, postural, and action tremor diagnostic of HT. Patient underwent right globus pallidus internus DBS surgery. At six month follow up, tremor rating scales showed 80% overall improvement with marked improvement in daily activities.
Figure 2
Axial (left) and sagittal (middle) T1 weighted MRI with gadolinium, and sagittal CT scan (right) of unsecured AV fistula.