A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 264,679 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers. Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses. Acute hemorrhagic necrotizing encephalopathy is associated to the cytokine storm. A frontal hypoperfusion syndrome has been identified. There are isolated reports of seizures, encephalopathy, meningitis, encephalitis, and myelitis. The neurological diseases affecting the PNS and muscle in COVID-19 are less frequent and include Guillain-Barré syndrome; Miller Fisher syndrome; polyneuritis cranialis; and rare instances of viral myopathy with rhabdomyolysis. The main conclusion of this review is the pressing need to define the neurology of COVID-19, its frequency, manifestations, neuropathology and pathogenesis. On behalf of the World Federation of Neurology we invite national and regional neurological associations to create local databases to report cases with neurological manifestations observed during the ongoing pandemic. International neuroepidemiological collaboration may help define the natural history of this worldwide problem.

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SUMMARY:Chikungunya, an alphavirus presenting with fever, rash, and polyarthritis, is derived from the Makonde word that means "that which bends up," in reference to the crippling manifestations of the disease. Most often it is a self-limiting febrile illness. Neurologic complications of Chikungunya infection have been reported. We are reporting the clinical and neuroimaging data in 2 patients with Chikungunya encephalomyeloradiculitis and brain autopsy findings in 1 patient. Chikungunya virus was first isolated in Calcutta, India, in 1963, 1 with several reported outbreaks in India since then. The first isolation of the disease worldwide was in 1952, following an outbreak on the Makonde Plateau. The symptoms include fever, headache, rash, and severe arthralgia. Many of these symptoms are indistinguishable from dengue fever, and simultaneous isolation of both dengue and Chikungunya from sera of patients has been reported.2 Chikungunya virus, an Old World alphavirus, is related antigenically to O'nyongnyong virus and is not known to be neurotropic. However, meningoencephalitis has been reported in outbreaks in India and the Reunion Islands. 3,4 We present the clinical, neuroimaging, and brain autopsy findings of Chikungunya encephalomyeloradiculitis, a relatively unknown and rare complication of the infection. Case Reports Case 1A 65-year-old man had low-grade fever and joint pain, which were treated with analgesics. A few days later he became drowsy. Findings of a complete blood analysis were normal. However, the patient's condition deteriorated clinically. On examination, he was semiconscious with neck rigidity, no limb movements, and an extensor plantar response. CSF analysis revealed elevated proteins, low sugars, and a few cells with lymphocyte predominance. CSF and serum were positive for immunoglobulin M (IgM) antibodies to Chikungunya virus. Intravenous methylprednisolone was administered for 5 days with 5 cycles of plasmapheresis. The patient was shifted to our hospital 45 days after the onset of symptoms. Electromyography (EMG) and nerve-conduction studies revealed acute generalized motor axonal neuropathy with no sensory component. Brain MR imaging revealed bilateral frontoparietal white matter lesions with restricted diffusion (Fig 1A), which enhanced on postcontrast T1-weighted (T1WI) fatsaturated images (Fig 1B). Spinal MR imaging revealed enhancement of the ventral cauda equina nerve roots (Fig 1C). He was administered IV dexamethasone and given supportive treatment; however, he did not improve clinically and was lost to further follow-up. Case 2A 73-year-old man had fever and joint pain, which were treated with analgesics. A few days later, he became drowsy and unresponsive with reduced limb movements. He was admitted 1 week after initial onset of symptoms. Examination revealed absent deep tendon reflexes with an extensor plantar response. CSF studies revealed increased cells (predominantly lymphocytes), elevated proteins, and low sugar. CSF and serum were positive for IgM antibodies to the Chikun...

reported on 214 patients who were admitted to hospital in Wuhan, China, with acute COVID-19. Symptoms were severe in 59% (mean age 58•7 years) of these patients, and non-severe in 41% (mean age 49•9 years). In total, 78 (36%) of 214 patients had neurological compromise, which was more common in severe (46%) than in non-severe (30%) cases and included stroke, impaired consciousness, myopathy, and neu ralgic pain. Viral meningo encephalitis with presence of SARS-CoV-2 in CSF by viral genome sequencing has been reported in patients in China 3 and Japan. 4 In the USA, a woman aged between 50 and 60 years developed COVID-19 and altered mental status. Brain MRI on this patient showed bilateral haemorrhagic rim-enhancing lesions within thalami, medial tem poral lobes, and subinsular regions char acteristic of acute haemorrhagic necrotis ing encephalopathy. 5 This con dition also, but rarely, occurs in influenza and other encephali tides in association with cytokine storm syndrome.Amid confronting a severe out break of COVID-19, the Spanish Neurological Society (Sociedad Española de Neurología) implemented a registry of neuro logical manifestations in patients with confirmed COVID-19. We applaud this initiative and propose to expand these efforts globally to define the nervous system involvement in COVID-19. The Environmental Neurology Specialty Group of the World Federation of Neurology (ENSG-WFN) is encouraging neurological soci eties around the world to develop national or regional neuroepidemiological data banks to report all cases of new-onset, acute, delayed, and any long-latency neurological disorders associ ated with SARS-CoV-2 infection during the COVID-19 pandemic. Late parkinsonism occurred among survivors of the 1918-20 influenza pandemic. Therefore, neurologists must be prepared for the occurrence of delayed neurological manifestations of COVID-19.

High and rising neutralizing antibody titers (NATs) to enterovirus type 70 (EV70) were detected in the serum and cerebrospinal fluid (CSF) of patients with polio-like motor paralysis accompanying acute hemorrhagic conjunctivitis (AHC) in an outbreak of AHC in 1981 in Bombay, India. Fifty-four (88.5%) of 61 patients with AHC with or without neurologic disease had serum NATs of greater than or equal to 1:16, and some paired sera from these patients showed significant increases in NAT. Serum from noninfected control subjects had no significant neutralizing antibody to EV70. Thirty-six (94.7%) of 38 CSF specimens from 30 patients with spinal or a combination of spinal and cranial motor paralysis associated with AHC had NATs ranging from 1:2 to 1:256. No neutralizing antibody was found in CSF specimens from patients with AHC alone or in those from non-infected control subjects, and a reduced ratio of serum NAT to CSF NAT was detected in patients with neurologic disease. Therefore, it is highly likely that intrathecal synthesis of antibody occurred in response to direct invasion of the central nervous system by EV70. The results represent strong laboratory evidence of the neurovirulence of EV70.