Despite rapid progress of therapeutic options for immune–mediated neuropathy (IMN), severe neurological sequelae or intractability still exist. These interfere patients' activity of daily living (ADL) and quality of life (QOL). Life style–related diseases such as hypertension and hyperlipidemia are very common, wide variety of medicines are subscribed daily for those suffering from life style–related diseases (life style drug).
Hydroxymethylglutaryl–CoA reductase inhibitors (statins) and angiotensin II receptor blockers (ARBs), popular life style drugs, additionally exhibit immune suppression ; firstly in animal model of multiple sclerosis although their effects of IMN remain vague. Thus we attempted to investigate the effect of atorvastatin (ATO), one of statins, on EAN. ATO suppressed motor paralysis of EAN mildly and intraneural expression of proinflammatory cytokine interferon–gamma (IFN). Besides, peak of anti–inflammatory cytokine interleukin (IL)–10 expression was also suppressed and delayed. We supposed that ATO might only suppress IFN, not upregulate IL–10, finally suppressed EAN. We then investigated the effect of various ARBs, candesartan (CAN), losartan (LO) and irbesartan (IRB) on EAN. IRB suppressed motor paralysis through entire EAN course while CAN did not suppress and LO delayed onset and accelerated recovery mildly. These differences clearly depended on the affinity to C–C chemokine receptor 2b that is main receptor for C–C chemokine CCL2 which attracts mononuclear phagocytes from blood stream to site of inflammation in peripheral nerve. These affinities can be estimated according to molecular data easily now a days.
Furthermore, in vivo experiments proved the efficacy and accuracy of the molecular modelling. This strategy might be powerful tool to identify unique drugs, formerly off–label common drug such as life style drugs.
COVID–19 is a highly infectious viral disease caused by the novel coronavirus SARS–CoV2. SARS–CoV–2 has spread rapidly all over the world and has affected various aspects of our life includming medicine and economic. Preliminary clinical data indicate that SARS–CoV–2 infection is associated with neurological and neuropsychiatric illness. COVID–19 can have impact on the brain in multiple ways, both directly and indirectly. We're facing with the era when we have to live together with COVID–19 and it's important to understand the characteristics of SAR–CoV–2. In this review, we summarize the mechanism in which COVID–19 causes neurological complications and what type of neurological and neuropsychiatric comorbidities occur in COVID–19 cases.
Coronavirus disease 2019 (COVID–19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2). This review summarizes the knowledge about SARS–CoV–2 immunology and discusses the policy of clinical practice for neuroimmune diseases at the time of the SARS–CoV–2 pandemic. The human defense systems against SARS–CoV–2 infection begin to work through innate immunity. Most neuroimmune diseases are caused by impairment of adaptive immunity, which preserves the function of innate immunity. Therefore, patients with neuroimmune diseases are not typically susceptible to COVID–19 and will not experience severe symptoms. However, patients with multiple sclerosis are at risk if their score on the Expanded Disability Status Scale is high. In the context of the COVID–19 pandemic, various neuroimmune disease practice guidelines have been published assessing the risk COVID–19 poses with each immunotherapeutic agent. Some immunotherapeutics may reduce immunity to viral infections. In particular, B–cell depletion therapy (rituximab, ocrelizumab, and inebilizumab) should be avoided because it can cause severe COVID–19 outcomes and decrease immune response to vaccination. On the other hand, some immunotherapeutics such as dexamethasone and tocilizumab may prevent severe COVID–19 symtpoms by suppressing cytokine storms. In most neuroimmune diseases, infection is known as a risk factor for acute exacerbation, so there is a risk of exacerbation of neuroimmune diseases by SARS–CoV–2 infection. In diseases such as myasthenia gravis, where respiratory function is impaired, COVID–19 has a high risk of being fatal. In addition to treatment of viral infections, these patients should be carefully monitored with immunotherapy. The efficacy and safety of COVID–19 vaccines in patients with neuroimmune diseases is still unclear and awaits further study.
Coronavirus disease 2019 (COVID–19) associated with SARS–CoV–2 virus infection is often associated with neuromuscular symptoms, although it is mainly characterized by respiratory symptoms. In this article, I present movement disorders associated with COVID–19 including myoclonus, tremor, parkinsonism, and ataxia. These findings are presumed to be caused by immune–mediated pathogenesis after infection. Because the reports on the effects of COVID–19 in the treatment of neurodegenerative diseases are almost limited to Parkinson's disease, the effects of COVID–19 on the motor and non–motor symptoms of Parkinson's disease and some important points to consider in clinical practice are presented.
Patients with dementia have been reported to have a higher risk of COVID–19 severity and mortality, especially in patients with more severe dementia. COVID–19 patients with dementia may exhibit non–respiratory symptoms such as delirium or diminished living function, even in the absence of obvious physical symptoms. These atypical symptoms of COVID–19 can reduce early awareness of the disease, increase the spread of COVID–19 to the people around. Although social distance and safeguard procedures remain to be the most effective approaches to prevent SARS–CoV–2 infection, problems unique to dementia patients have also been pointed out. In patients with dementia, changes in the environment caused by COVID–19 pandemic often cause behavioral psychological symptoms to appear or worsen and cognitive functioning to decline. It is important for health–care providers involved in dementia care to collaborate with multiple disciplines depending on the dementia patient's life situation, and to strive to prevent infection and maintain cognitive and living functions of them.
Perfect defense from SARS–CoV–2 infection prioritize in triaging acute stroke patients during COVID–19 pandemic. On April 2020, Japan Stroke Society urgently announced protected code stroke, JSS–PCS, informing all medical staffs the need to know the essential requirement. Patients under investigation should be accepted with PCS manner. The points of proposed PCS are (1) wearing reliable PPE, (2) wearing surgical mask on the patient, and (3) response with the minimum required number of personnel. It is strongly recommended to prepare individualized protocol of PCS in each stroke center.
What is important during this COVID–19 pandemic, are summarized as follows. (1) sharing and effective use of information regarding regional healthcare system provision, (2) achieving effective measures to reduce the number of COVID–19 cases, and (3) sharing of information, including countermeasures against nosocomial infection, between medical institutions providing emergency treatment for stroke.
Many patients with neuromuscular disease are involved in respiratory insufficiency. It becomes difficult problem especially in those patient with COVID–19. There are 7 important factors for the respiratory care in this condition. Those are risk of aerosol, care plan for non–invasive positive pressure ventilation and tracheostomy invasive positive pressure ventilation, tips of suction, oxygen therapy, mechanical clearance of tracheal air way and rehabilitation technique of respiratory care.
The risk of aerosol might be the most important for every other 6 factors. I informed each factor precisely. It should be useful for daily clinical setting.
COVID–19 pandemic has huge impact on rehabilitation medicine and rehabilitation services. The impact is sorted to two types. One is neuromuscular disease newly caused by COVID–19 and the other is an adverse effect on people with pre–existing neuromuscular diseases.
COVID–19 is ACE–2 receptors where SARS–COV–2 virus sticks and invades are distributed vascular endothelial cells. Multi–organ failure by COVID–19 result may result in encephalopathy, thrombotic condition may induces Stroke. Encephalitis may be occurred from direct invasion of SARS–COV–2 virus. Cases with Guillain–Barré syndrome are reported by immune reaction to this virus. Rhabdomyolysis during COVID–19 is also reported, but the mechanism is not known. The approaches and methods of rehabilitation to these diseases are common with those to neuromuscular diseases by other etiologies. Neurorehabilitation has to be planned early phase of disorders, but we should be careful to prevent infection of COVID–19 to medical doctors and medical stuffs.
The impact of COVID–19 pandemic is enormous to the people with pre–existing neuromuscular diseases. Voluntary restraint of outgoing is requested by Japanese government more than one month. Fear to be infected is inflated by mass media. Times to visit hospitals and opportunity to have rehabilitation service were markedly decrease during COVID–19 pandemic. The decreased activity brought physical and mental hypofunction. Neurorehabilitation service should be reconstructed to prevent more deterioration. During pandemic of COVID–19, telerehabilitation is good candidate to provide rehabilitation service safely.
The current COVID–19 pandemic is catalyzing the use of telemedicine all over the world. Teleneurology, which defined as telemedicine use in neurology area, is one of solution for vulnerable patients with chronic neurological diseases require a specialist's care even in such a situation to avoided non–urgent hospital visits. In this review, currently available technologies, obstacles and future potential of telenueorology will be discussed.
A 42–year–old Japanese man was admitted to our hospital with numbness, weakness of the extremities, and gait disturbance, following watery diarrhea during long–term detention. Neurological examination revealed areflexia, muscle weakness, and hyperalgesia predominantly in the distal extremities. Nerve conduction study revealed motor and sensory axonal neuropathy. The initial diagnosis was acute motor sensory axonal neuropathy subtype of Guillain–Barré syndrome (GBS). Because of renal dysfunction and hyperkalemia, we performed immunoadsorption plasmapheresis, with the addition of hemodialysis, as immunotherapy. After completing the first treatment course, he suddenly developed dyspnea due to heart failure and went into cardiogenic shock. There was no evidence of pulmonary thrombotic embolism on chest computed tomography. During the clinical course, serum vitamin B1 level was found to be low, and he was finally diagnosed as having peripheral neuropathy and heart failure due to beriberi with vitamin B1 deficiency. The heart failure and neurological symptoms gradually resolved with vitamin administration. In this case, extracorporeal circulation induced shoshin beriberi, which is characterized by severe cardiac failure. This case highlights the need to consider beriberi as a differential diagnosis in cases with clinical manifestation suggestive of GBS.
We report three cases of amyotrophic lateral sclerosis in which long–term intermittent gait training was performed using a hybrid assistive limb (HAL). There were no adverse events related to HAL and gait speed improved in a saw tooth–like pattern during gait training with a high frequency. In addition, we performed endoscopic gastrostomy on two patients due to the deterioration of bulbar palsy ; however, gait training was resumed without adverse events related to gastric fistula by paying attention to decompression of the gastric fistula and gastrostomy button.
A 71–year–old man presented with dizziness and gait disturbance. On admission, his Scale for Assessment and Rating of Ataxia (SARA) score was 21. Cerebrospinal fluid examination revealed five oligoclonal bands. Although magnetic resonance imaging (MRI) of the brain showed slight cerebellar atrophy, and single–photon emission computed tomography (SPECT) showed no reduction in cerebellar blood flow. Computed tomography (CT) of the chest showed a lesion at the S6 area of the left inferior lobe. Fluorodeoxyglucose positron emission tomography (FDG–PET) demonstrated abnormal 18F–FDG uptake not only in this lesion, but also in the tracheal bifurcation and left adrenal gland. Bronchoscopic biopsy of the tracheal bifurcation lesion revealed combined small cell carcinoma. Blood examination revealed anti–P/Q–type voltage–gated calcium channel (VGCC) antibodies, and he was diagnosed with paraneoplastic cerebellar degeneration associated with lung small cell carcinoma. He was started on chemotherapy for lung small cell carcinoma and given an intravenous injection of immunoglobulin for cerebellar ataxia. After one year, a CT scan of the chest showed that the tumors had disappeared completely, but his cerebellar ataxia remained almost unchanged, and anti–VGCC antibodies were still detected in his blood. Plasma exchange and steroid pulse therapy did not help his cerebellar ataxia. His SARA score changed from 21 to 20.5 during the 5 years since the onset of the disease.
A 76–years–old woman who had bacterial meningitis caused by chronic sinusitis of the left sphenoid sinus. Her condition was improved by antibiotic treatment and she was discharged. She underwent endoscopic sinus surgery type V and transnasal endoscopic repair for cerebrospinal fluid leaks, but one month after the operation, fever at 37°C level and slight recurrent neck pain recurred. She had a slight stiff neck. Cell counts and protein quantitation were elevated, sugars were reduced in cerebrospinal fluid. Pseudomonas aeruginosa was positive in cerebrospinal fluid culture.
We report a case of recurrent bacterial meningitis despite after transnasal endoscopic repair for cerebrospinal fluid leaks.