Severe acute respiratory syndrome
SARS broke out in Hong Kong, Taiwan, Canada, and other locations in 2003. It has been reported to be associated with encephalitis, ischemic stroke, and polyneuropathy [35]. Seizures have been mentioned as the first symptom of SARS-related encephalitis [36]. In a necropsy study of eight patients who died of SARS, there was evidence of SARS-CoV infection in the brain cortex and hypothalamus [37]. Particles from the SARS-CoV virus have been found in the brains of patients infected with SARS, most frequently in brain neurons [37–39]. Murine studies found that intranasal injections of both MERS-CoV and SARS-CoV could enter the brain, presumably via the olfactory nerves [40,41]. Among the areas of the brain infected, the brain stem was a primary, but not exclusive, target for both MERS-CoV [41] and SARS-CoV [40,42].
Neurological sequelae of SARS have been only sporadically reported. Acute olfactory neuropathy has been reported in a case study of a 27-year-old female SARS patient who was diagnosed with SARS in 2003, hospitalized, and recovered with combination therapy of antiviral therapy (ribivarin plus steroids) [43]. Fever persisted for about three weeks from onset of symptoms. She was discharged from the hospital at around the same time she reported the paroxysmal bilateral loss of her sense of smell. An otolaryngologic examination, biochemistry tests, and subsequent magnetic resonance imaging scans showed nothing unusual with no lesions that might account for her loss of olfaction. Now 2 years after her recovery from SARS, she still has not regained her sense of smell [43]. The common causes of anosmia include structural defects in the nasal cavity or sinuses, head injury, brain trauma, brain lesions, or drug-induced loss of olfaction, and in her case, these could all be ruled out. It was postulated that her anosmia was a coronavirus-induced form of olfactory neuropathy [43].
Neuromuscular symptoms associated with SARS have also been reported. A 51-year-old woman in Taiwan developed probable SARS shortly after her husband was diagnosed [44]. She was hospitalized and intubated and had no evidence of respiratory syncytial virus; however, a bone-marrow biopsy showed evidence of infection-related hemophagocytic syndrome. Her condition gradually improved and she was extubated, but she complained of weakness, numbness, and paresthesia in her legs. Ten days after extubation, a neurological examination showed good mental clarity with intact cranial nerves, but symmetric loss of muscle strength in her legs and mild weakness in the hands. These conditions improved slowly and two months later, a neurological examination reported only mild loss of leg strength and slight numbness in the toes of her right foot [44].
A case report from Hong Kong describes a 59-year-old woman with severe SARS who developed status epilepticus; evidence of the virus was found in her cerebrospinal fluid [45]. Another case report describes a pregnant patient with SARS who experienced a generalized convulsion with suspected nervous system invasion by the virus [46].
The neurological manifestations observed in SARS include peripheral axonal neuropathy and elevated muscle enzymes, which might be caused by extensive virus-driven vasculitis [38,47]. These were considered to be polyneuropathic and/or myopathic symptoms associated with critical illness [47].