Asuka Nakajima

Posterior Subthalamic Area Deep Brain Stimulation for Fragile X–Associated Tremor/Ataxia Syndrome

To the Editor: Fragile X–associated tremor/ataxia syndrome (FXTAS) is an adultonset hereditary neurodegenerative disease underpinned by expansion of the premutation in the CGG trinucleotide repeats in the fragile mental retardation gene 1 (FMR1) (1). The prevalence of the FMR1 premutation is approximately 1/250 in women and 1/800 in men. Therefore, while the prevalence of FXTAS in men is estimated to be approximately 1 in 3000 to 6000 in general population, the prevalence in women is thought to be much lower (1,2). The syndrome clinically presents with postural and action tremors, cerebellar ataxia, cognitive deficits, parkinsonism, dysautonomia, and neuropathy (3), although exact manifestations can be variable among sufferers. Although there is not enough evidence of treatment for FXTAS, tremor in FXTAS can be treated with medications such as primidone, beta blockers, benzodiazepines, and memantine (4). Hall et al. reported that 50% of patients had mild to moderate improvement on primidone, that 37.5% had moderate improvement on beta blockers, and that 25% had moderate improvement on benzodiazepines (4). In patients with medication refractory FXTAS-associated tremor, ventral intermediate (Vim) nucleus of the thalamus deep brain stimulation (DBS) has been applied (5–10). Out of eight cases of Vim DBS, two have resulted in the worsening of balance and ataxia symptoms (5,10). Recently, posterior subthalamic area (PSA) stimulation has been suggested as an alternative option for control of severe tremor beyond essential tremor (ET) (11). Although there is no consensus to date regarding the best DBS target for patients with FXTAS, there has been a concern that the traditional Vim target would provide insufficient benefit, especially in cases of proximal tremor. We conducted a retrospective chart review of a single case of PSA DBS for a patient with the FXTAS mutation. This study was approved by the Institutional Review Board of Juntendo University School of Medicine.

Progressive transcortical sensory aphasia and progressive ideational apraxia owing to temporoparietal cortical atrophy

BackgroundIn contrast to frontotemporal lobar degeneration, atrophy of the focal posterior lateral cortex has not been thoroughly studied. Three clinical types of focal cortical atrophy have been described: 1) logopenic variant of primary progressive aphasia, which presents with impaired repetition despite normal articulation; 2) posterior cortical atrophy, which presents with prominent visuospatial deficits; and 3) primary progressive apraxia. All three clinical types are characterized by specific patterns of hypometabolism/hypoperfusion: the left posterior perisylvian area in the logopenic variant of primary progressive aphasia, bilateral parietooccipital areas in posterior cortical atrophy, and the parietal cortex in primary progressive apraxia. However, not every patient clearly fits into one of these categories.Case presentationHere we describe two patients with atypical focal cortical presentations. They presented with a history of a few years of progressive transcortical sensory aphasia characterized by fluent output with normal grammar and syntax, normal repetition, sentence comprehension deficits, and anomia without loss of word meaning. They also presented with progressive apraxia that began at the initial stages. Some forms of posterior symptoms including acalculia, agraphia, and visuospatial deficits were also observed. Hypoperfusion was noted mainly in the left temporoparietal region, which is slightly posterior to the perisylvian area.ConclusionsAlthough our cases lack in CSF findings and PIB scan, these two cases and previous reports might suggest the existence of a subgroup of patients presenting with transcortical sensory aphasia, apraxia, and posterior symptoms (acalculia, agraphia, and visuospatial deficits) in the setting of Alzheimer’s disease. This subgroup may reflect the spectrum of clinical manifestations between logopenic variant of primary progressive aphasia and posterior cortical atrophy.

Acute transient freezing of gait in a patient with posterior reversible encephalopathy syndrome

BackgroundPosterior reversible encephalopathy syndrome (PRES) is a transient clinical and neuroradiologic syndrome caused by cerebral vasogenic edema. Various reversible neurologic symptoms were shown in patients with PRES. Freezing of gait (FOG) is mainly observed in neurodegenerative diseases.Case presentationWe report a 43-year-old man, with undergoing hemodialysis therapy for chronic renal failure, had mild elevation of blood pressure. His consciousness level suddenly deteriorated, and brain MRI demonstrated hyperintense lesions in the bilateral basal ganglia on fluid-attenuated inversion recovery images, diffusion-weighted images, and apparent diffusion coefficient maps. After improvement of disturbance of consciousness, he showed FOG accompanied by bradykinesia and postural instability. His FOG spontaneously improved concurrently with alleviation of basal ganglionic lesions on follow-up MRI.ConclusionsIt is suggested that vasogenic edema on bilateral basal ganglia associated with PRES can cause acute transient FOG.

Current Topics in Deep Brain Stimulation for Parkinson Disease

There is a long history of surgical treatment for Parkinson disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment option for patients with medically refractory PD. However, there are still many problems and controversies associated with DBS. In this review, we discuss current issues in DBS for PD, including patient selection, clinical outcomes, complications, target selection, long-term outcomes, management of axial symptoms, timing of surgery, surgical procedures, cost-effectiveness, and new technology.

Subthalamic nucleus and globus pallidus interna influence firing of tonically active neurons in the primate striatum through different mechanisms

Both the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) are major targets for neuromodulation therapy for movement disorders. An example of such a therapy is deep brain stimulation (DBS). The striatum is the primary target for pharmacological treatment of these disorders. To further our understanding of both the functional relationships among motor nuclei and the mechanisms of therapies for movement disorders, it is important to clarify how changing the neuronal activity of one target, either by medication or by artificial electrical stimulation, affects the other connected nuclei. To investigate this point, we recorded single‐unit activity from tonically active neurons (TANs), which are putative cholinergic interneurons in the striatum, of healthy monkeys (Macaca fuscata) during electrical stimulation of the STN or GPi. Both STN stimulation and GPi stimulation reduced the TAN spike rate. Local infusion of a D2 receptor antagonist in the striatum blocked the reduction in spike rate induced by STN stimulation but not that induced by GPi stimulation. Further, STN stimulation induced phasic dopamine release in the striatum as revealed by in vivo fast‐scan cyclic voltammetry. These results suggest the presence of multiple, strong functional relationships among the STN, GPi, and striatum that have different pathways and imply distinct therapeutic mechanisms for STN‐ and GPi‐DBS.

Troubleshooting in hospitalized Parkinson's disease patients with a history of deep brain stimulation of the subthalamic nucleus

Deep brain stimulation is a treatment option for patients with Parkinsons disease who have motor complications, such as wearing off and dyskinesia. However, in some cases, the benefits of deep brain stimulation seem to diminish over time.

Delusional misidentification of inanimate objects, persons, and places after a left orbitofrontal cortex injury

Delusional misidentification, a condition in which a patient consistently misidentifies persons and places, rarely involves inanimate objects. Only two previous reports have described delusional misidentification of inanimate objects, which was causedby traumatic brain injury in one case (Abbate et al., 2012) and by delusional disorders in the other (Castillo & Berman, 1994). A neural basis was suggested in the case presented by Abbate et al. (2012), as the individual had right temporal lobe damage, although there must also have been diffuse axonal injury due to the nature of the traumatic brain injury. Here we describe a patient who presented with remarkable delusional misidentification of inanimate objects along with misidentification of persons and places after focal left orbitofrontal cortex damage due to subarachnoid hemorrhage. The patient was a 61-year-old right-handed man with 12 years of education. He had no past history of neurological or psychiatric diseases. He suffered rupture of an anterior communicating artery aneurysm (Hunt and Kosnik III), which was clipped. A ventriculoperitoneal shunt was placed to treat hydrocephalus. He was admitted to a rehabilitation unit 2 months post-onset, where, although he was alert, he frequently confabulated and tried to go to work or acted as if he was working. Because of substantial behavioral symptoms, he was then moved to the neuropsychiatric unit, where he continued to receive physical, occupational, and linguistic rehabilitation. Upon neurological examination, he showed no palsy or sensory deficits, and his daily activities in the hospital were almost independent. He scored 33/36 on Ravens Colored Progressive Matrices (compared with 29.2 ± 5.4 in 60 sec for normal controls) (Sugishita & Yamazaki, 1993), suggesting he had normal intelligence. In contrast, he scored only 3/12 on the Japanese version of the Rivermead Behavioural Memory Test (cut-off score of 7 for 60 sec) (Watanuki, Hara, Miyamori, & Etoh, 2002) and 12/18 on the Japanese version of the Frontal Assessment Battery (compared with 14.6 ± .9 in 60 sec for normal controls) (Kugo et al., 2007), which reflected his episodic memory deficits and frontal dysfunction. His performance on the logical memory of Wechsler Memory Scale-Revised (Sugishita, 2001) was <2% in comparison with the percentiles for the healthy groups, in which he confabulated that eggs were broken by a traffic

Attentional dysfunction and word-finding difficulties are related to semantic jargon after a thalamic lesion: a case report

ABSTRACT Background: Although many case reports on neologistic jargon have been documented, reports on semantic jargon are extremely rare, suggesting that semantic jargon may occur more rarely than neologistic jargon. Aims: To investigate potential mechanisms underlying semantic jargon. Methods & Procedures: We describe a patient who presented with semantic jargon after a left thalamic hemorrhage that mainly affected the pulvinar, lateral posterior nucleus, centromedian nucleus, and reticular nucleus. She was followed for 8 years, during which the temporal changes in her linguistic and neuropsychological functions were investigated. Outcomes & Results: The patient’s semantic jargon disappeared and selective attention improved in parallel. Word-finding deficits remained at the end of the observation period. Conclusions: Our observations of this patient suggest that a thalamic lesion can cause attentional and linguistic dysfunction that does not activate an intended word and its images and, conversely, fails to inactivate non-relevant words and associated images, resulting in semantic jargon.

Interleaving stimulation with a combination of bipolar and monopolar configurations for secondary failure of bilateral subthalamic stimulation in Parkinson's disease

Current control technology using interleaving stimulation could be theoretically useful for maximizing the benefits of deep brain stimulation, but it is seldom reported. A 61‐year‐old man with young‐onset Parkinsons disease was previously treated with bilateral subthalamic nucleus deep brain stimulation because of wearing‐off and peak‐dose dyskinesia; he again developed wearing‐off and a gait disturbance 3 years after surgery. His deep brain stimulation was adjusted by utilizing interleaving stimulation with a combination of monopolar and bipolar configurations, because increasing stimulation with single or double monopolar stimulation, and interleaving monopolar stimulation caused pyramidal side‐effects. After adjusting deep brain stimulation, his wearing‐off symptoms and gait disturbance were markedly improved without any side‐effects. The present case report describes the potential of interleaving stimulation with a combination of monopolar and bipolar settings for the treatment of Parkinsons disease.

Rescue pallidal stimulation for diphasic and stimulation-induced dyskinesia after successful subthalamic stimulation for Parkinson's disease

A 64‐year‐old woman with Parkinsons disease who developed motor fluctuations, and both levodopa‐induced and stimulation‐induced dyskinesia, after long‐term treatment of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), underwent implantation of additional globus pallidus internus (GPi) DBS leads. Although an appropriate DBS target should be chosen, “rescue” GPi DBS can synergistically work with pre‐existing STN DBS for the treatment of dyskinesia, which might provide a “third honeymoon.”