Levodopa treatment and dendritic spine pathology.

Parkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective treatment for the motor symptoms of PD. However, chronic oral levodopa treatment can lead to various motor and nonmotor complications because of nonphysiological pulsatile dopaminergic stimulation in the brain. Examinations of autopsy cases with PD have revealed a decreased number of dendritic spines of striatal neurons. Animal models of PD have revealed altered density and morphology of dendritic spines of neurons in various brain regions after dopaminergic denervation or dopaminergic denervation plus levodopa treatment, indicating altered synaptic transmission. Recent studies using rodent models have reported dendritic spine head enlargement in the caudate-putamen, nucleus accumbens, primary motor cortex, and prefrontal cortex in cases where chronic levodopa treatment following dopaminergic denervation induced dyskinesia-like abnormal involuntary movement. Hypertrophy of spines results from insertion of alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid receptors into the postsynaptic membrane. Such spine enlargement indicates hypersensitivity of the synapse to excitatory inputs and is compatible with a lack of depotentiation, which is an electrophysiological hallmark of levodopa-induced dyskinesia found in the corticostriatal synapses of dyskinetic animals and the motor cortex of dyskinetic PD patients. This synaptic plasticity may be one of the mechanisms underlying the priming of levodopa-induced complications such as levodopa-induced dyskinesia and dopamine dysregulation syndrome. Drugs that could potentially prevent spine enlargement, such as calcium channel blockers, N-methyl-D-aspartate receptor antagonists, alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid receptor antagonists, and metabotropic glutamate receptor antagonists, are candidates for treatment of levodopa-induced complications in PD. © 2017 International Parkinson and Movement Disorder Society.

Dermatomal Sensory Manifestations in Opalski Syndrome.

A 31-year-old Japanese woman presented with sudden-onset unstable gait followed by nuchal pain. A neurological examination revealed right-sided limb weakness and decreased pain and thermal sensation on the left side below the level of the L1 dermatome. A lower lateral medullary infarction with ipsilateral hemiplegia, known as Opalski syndrome, caused by spontaneous vertebral artery dissection was diagnosed by magnetic resonance imaging. The spinothalamic tract in the medulla oblongata has a topographic arrangement of sensory fibers, and the dermatomal sensory deficit in this case can be explained in relation to that. This is the first reported case of Opalski syndrome with dermatomal sensory manifestations. Opalski syndrome could be a differential diagnosis for dermatomal sensory manifestations.

Elevated pain threshold in patients with asymptomatic diabetic neuropathy: an intraepidermal electrical stimulation study.

INTRODUCTION: The loss of epidermal nerve fibers is regarded as an early pathological change in human diabetes. We investigated epidermal Aδ nerve fiber function by examining pain threshold by means of intraepidermal electrical stimulation (IES) in early diabetic neuropathy. METHODS: We recruited 20 asymptomatic diabetic patients. Eighteen age-matched, healthy subjects served as controls. We placed the IES electrode onto the skin of the foot dorsum and delivered weak electrical stimulation. We defined pain threshold as the minimum electrical intensity at which a subject felt a pricking sensation. RESULTS: The mean pain thresholds in the patient group were significantly higher (0.053 ± 0.036 mA; P < 0.01) than in the control group (0.027 ± 0.006 mA). CONCLUSION: We confirmed that the pain threshold was elevated in early diabetic neuropathy. We conclude that the IES electrode is a useful tool to evaluate early diabetic polyneuropathy. Muscle Nerve 54: 146-149, 2016.

Effect of educational television commercial on pre-hospital delay in patients with ischemic stroke.

Administering intravenous recombinant tissue plasminogen activator (r-tPA) within 4.5 h or endovascular procedures within 8 h of ischemic stroke onset may reduce the risk of disability. The effectiveness of media campaigns to raise stroke awareness and shorten pre-hospital delay is unclear. We studied 1144 consecutive ischemic stroke patients at Aomori Prefectural Central Hospital, Japan, between March 2010 and February 2014. From March 2012, the government sponsored an educational campaign based on a television commercial to improve knowledge of stroke symptoms and encourage ambulance calls for facial palsy, arm palsy, or speech disturbance. For the 544 and 600 patients admitted before and during the intervention, respectively, we recorded the National Institutes of Health Stroke Scale score, stroke type, the time when patients or bystanders recognized stroke symptoms, and hospital arrival time. Pre-hospital delay, as the time interval from awareness of stroke to hospital arrival, was categorized as 0-3, 3-6, and 6+ h. The mean pre-hospital delay was shorter (12.0 vs 13.5 h; P = 0.0067), the proportion of patients arriving within 3 h was larger (55.7 vs 46.5 %; P = 0.0021), and the proportion arriving after 6 h was smaller (32.7 vs 39.5 %; P = 0.0162) in the intervention group than in the pre-intervention group. There was no significant difference in the proportion of patients treated with r-tPA (6 and 7.5 % of the intervention and pre-intervention groups, respectively). A television-based public education campaign potentially reduced pre-hospital delay for ischemic stroke patients, but the r-tPA treatment rate was unchanged.

Morphologic changes of dendritic spines of striatal neurons in the levodopa-induced dyskinesia model.

Maladaptive plasticity at corticostriatal synapses plays an important role in the development of levodopa-induced dyskinesia. Recently, it has been shown that synaptic plasticity is closely linked to morphologic changes of dendritic spines. To evaluate morphologic changes of dendritic spines of two types of striatal medium spiny neurons, which project to the internal segment of globus pallidus or the external segment of globus pallidus, in the levodopa-induced dyskinesia model, we used 6-hydroxydopamine-lesioned rats chronically treated with levodopa. Dendritic spines were decreased and became enlarged in the direct pathway neurons of the model of levodopa-induced dyskinesia. The same levodopa treatment to normal rats, in which no dyskinesia was observed, also induced enlargement of dendritic spines, but not a decrease in density of spines in the direct pathway neurons. These results suggest that a loss and enlargement of dendritic spines in the direct pathway neurons plays important roles in the development of levodopa-induced dyskinesia.

An autopsy case of meningeal carcinomatosis with parenchymal invasion through the cranial and spinal nerve roots.

Meningeal carcinomatosis is a well-known complication of malignant neoplasms. We report a case of meningeal carcinomatosis of 2 months' duration in a 22-year-old man, in whom the initial symptom was gradually worsening headache. Postmortem examination revealed infiltrating adenocarcinoma of the stomach. Carcinoma cells showed diffuse spread to the subarachnoid space of the brain and spinal cord. In many places, subarachnoid tumor cells had infiltrated to the cranial and spinal nerves. Moreover, carcinoma cells in the nerve roots extended to the parenchyma of the brain and spinal cord beyond the CNS-peripheral nervous system junction. These findings suggest that cranial and spinal nerve roots can be a possible route of parenchymal invasion in meningeal carcinomatosis.

Ulnar nerve palsy-like motor and sensory loss caused by a small cortical infarct.

A 56-year-old man with a small infarct in the left precentral knob area induced both motor and sensory impairments that were similar to right ulnar nerve palsy. The only difference from ulnar nerve palsy was that the patient showed sensory disturbance not only on the ulnar side but also on the radial side of the right ring finger.

A Long Interval from a Spinal Cord Lesion to a Subsequent Brain Lesion in Primary Central Nervous System Vasculitis.

Primary central nervous system vasculitis (PCNSV) is an uncommon vasculitis restricted to the small- and medium-sized vessels in the brain and spinal cord. Previously, only 9 cases have been reported that initially manifested as an isolated spinal cord lesion with subsequent brain involvement, where the longest interval from the onset to brain involvement was 1 year and 11 months. We herein report the case of an isolated spinal cord lesion with subsequent brain involvement appearing seven years and five months later. This case shows that brain lesions can develop after an extended interval from spinal onset in PCNSV.

Evaluation of cerebral blood flow in older patients with status epilepticus using arterial spin labeling.

INTRODUCTION: Although older patients with status epilepticus (SE) have a high mortality rate and poor outcome, it is difficult to perform emergent electroencephalography (EEG) to diagnose SE in community hospitals. Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) technique that can rapidly assess cerebral blood flow (CBF). Further, ASL can detect increased CBF in the ictal period. Therefore, ASL may be a useful tool for diagnosing SE in older patients. However, its effectiveness in this population is unknown. METHODS: We retrospectively investigated differences in CBF abnormalities between older patients (≥70 years) and non-older patients (<70 years) with SE using ASL. Participants were diagnosed with convulsive status epilepticus (CSE) or non-convulsive status epilepticus (NCSE) based on symptoms, brain MRI, and EEG. RESULTS: ASL detected CBF abnormalities in 40% of older patients with CSE or NCSE. Rates of CBF abnormalities in older patients were not significantly different compared with that in non-older patients. CONCLUSIONS: ASL did not detect a higher rate of CBF abnormalities in older patients, but may help physicians diagnose SE in older patients in a community hospital setting if emergent EEG cannot be immediately performed.

Morphological dendritic spine changes of medium spiny neurons in the nucleus accumbens in 6-hydroxydopamine-lesioned rats treated with levodopa.

The mechanisms of dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) remain unclear, although it is known that the nucleus accumbens (NAc) plays a role in its development. Based on the hypothesis that DDS and levodopa-induced dyskinesia (LID) share a pathophysiological basis, we investigated dendritic spine morphology of medium spiny neurons (MSNs) in the NAc of a rat model of LID, because spine enlargement in MSNs of the caudate/putamen has been proposed to be a morphological hallmark of LID. Spines of NAc MSNs also became enlarged in the LID model. This result suggests that excitatory supersensitivity of MSNs in the NAc is involved in the development of DDS, similar to what occurs in the caudate/putamen in LID.

LSVT-BIG Improves UPDRS III Scores at 4 Weeks in Parkinson's Disease Patients with Wearing Off: A Prospective, Open-Label Study.

The efficacy of LSVT-BIG for advanced Parkinson's disease (PD) patients with wearing off remains to be determined. Therefore, we evaluated whether LSVT-BIG improves motor disability in eight PD patients with wearing off. Unified Parkinson's Disease Rating Scale (UPDRS) scores, daily off time, and mobility assessments were evaluated during the "on" time before and after the LSVT-BIG course. LSVT-BIG significantly improved UPDRS III scores at 4 weeks and UPDRS II scores in the "off" state at 12 weeks, with no changes in the other measures. The findings suggest that LSVT-BIG may be an effective therapy for advanced PD patients with wearing off.

Utility of nerve conduction studies for diagnosis of injury to the medial branch of the superficial radial nerve.

INTRODUCTION: The clinical utility of nerve conduction study (NCS) for the distal medial branch of the superficial radial nerve (SRN) has not yet been clarified. Therefore, we investigated the clinical utility of NCS in patients with suspected SRN injury and compared the results with those in healthy control subjects. METHODS: Bilateral NCS of the medial branch of the SRN was performed in two patients with suspected injury of the medial branch of the SRN, and in 20 healthy control subjects. A surface recording electrode was placed at the medial side of the metacarpophalangeal joint of the thumb. The SRN was then stimulated at a location 12 cm proximal from the recording electrode. RESULTS: The mean sensory nerve action potential in the two patients was significantly lower than that of the controls (6.75 ± 0.92 vs. 23.8 ± 8.2 µV, P < 0.05). The side-to-side differences in sensory nerve action potential in the two patients were significantly higher than in the controls (55 ± 7.1 vs. 11 ± 7.8%, P < 0.05). CONCLUSIONS: NCS may be useful for diagnosing injury of the medial branch of the SRN.

Hypertrophic pachymeningitis accompanying neuromyelitis optica spectrum disorder: A case report.

We report a case of idiopathic cerebral hypertrophic pachymeningitis accompanying neuromyelitis optica spectrum disorder. No other identifiable cause of pachymeningitis was detected. Corticosteroid therapy was effective for both diseases. Hypertrophic pachymeningitis is closely related to autoimmune inflammatory disease of the central nervous system. This case supports the hypothesis that hypertrophic pachymeningitis can be a rare comorbidity of neuromyelitis optica spectrum disorder.

Amyotrophic lateral sclerosis with demyelinating neuropathy.

Amyotrophic lateral sclerosis (ALS) with demyelinating polyneuropathy is a rare condition. We describe two ALS patients with demyelinating neuropathy. Immunomodulatory therapies brought slight symptomatic benefits to the patients, but the treatments could not halt the progression of ALS. Chance coincidence of the two diseases is unlikely in view of the low prevalence. ALS, mainly consisting of progressive axonal degeneration, might show temporal demyelinating features of peripheral nerves both electrophysiologically and pathologically. The pathomechanism for the demyelination in ALS remains to be elucidated.