The Neurohospitalist

Patients admitted to the hospital with neurological problems are sometimes incapacitated and unable to make end-of-life decisions. In these instances, without an advanced directive from the patient, clinicians and family members must make critical medical decisions without input from the patient. This paper looks at two cases - one child and one adult – in which neuroprognosis was uncertain, and physician and family members’ beliefs on end-of-life care clash. We provide insight into these disagreements and reflect on how best to manage them. We argue that when considering withdrawing treatment, respecting autonomy is of paramount importance, while decision-making about continuing life-sustaining treatment requires clinicians to ensure surrogates are adequately educated about the principle of beneficence.

The grim circumstances of the COVID-19 pandemic have highlighted the need to refine and adapt stroke systems of care. Patients’ care-seeking behaviors have changed due to perceived risks of in-hospital treatment during the pandemic. In response to these challenges, we optimized a recently implemented, novel outpatient approach for the evaluation and management of minor stroke and transient ischemic attack, entitled RESCUE-TIA. This modified approach incorporated telemedicine visits and remote testing, and proved valuable during the pandemic. In this review article, we provide the evidence-based rationale for our approach, describe its operationalization, and provide data from our initial experience.

We report the case of a healthcare worker who presented with a large vessel acute ischemic stroke in setting of a mild SARS-CoV-2 infection and provide a review of the emerging literature on COVID-related stroke. A 43-year-old female presented with right-sided hemiparesis, aphasia and dysarthria. She had a nonproductive of cough for 1 week without fever, fatigue or dyspnea. A CT Head, CT angiography and CT perfusion imaging revealed a M1 segment occlusion of the left middle cerebral artery requiring transfer from a primary to a comprehensive stroke center. A nasopharyngeal swab confirmed SARS-CoV-2 infection prior to arrival at the accepting center. During the thrombectomy a 3 cm thrombus was removed. Thrombus was also evident in the 8 French short sheath during closure device placement so a hypercoagulable state was suspected. Stroke work-up revealed a glycosylated hemoglobin of 8.7%, elevation of inflammatory markers and an indeterminate level of lupus anticoagulant IgM. On discharge home, she had near complete neurological recovery.

This case highlights suspected mechanisms of hypercoagulability in SARS-CoV-2 infection and the importance of optimizing stroke care systems during the COVID-19 pandemic.

Spontaneous intracranial hypotension (SIH) still remains an underdiagnosed etiology of new-onset headache. Important risk factors include chiropractic manipulation (CM). We present a case of a 36-year-old Filipino woman who presented with severe bifrontal and postural headache associated with dizziness, vomiting, and doubling of vision. A cranial computed tomography scan was done which showed an acute subdural hematoma (SDH) at the interhemispheric area. Pain medications were given which afforded minimal relief. On history, the headaches occurred 2 weeks after cervical CM. Cranial and cervical magnetic resonance imaging revealed findings supportive of intracranial hypotension and neck trauma, respectively. The patient improved with conservative management. We found 12 articles on SIH and CM after a systematic review of literature. Eleven patients (90.9%) initially presented with orthostatic headache. Eight patients (66.7%) were initially treated conservatively but only 5 (62.5%) had complete recovery. Recovery was achieved within 14 days from start of supportive therapy. Among the 3 patients who failed conservative treatment, 2 underwent non-directed epidural blood patch and one required neurosurgical intervention. This report highlights that a thorough history is warranted in patients with new onset headache. A history of CM must be actively sought. The limited evidence from the case reports showed that patients with SIH and SDH but with normal neurologic examination and minor spinal pathology can be managed conservatively for less than 2 weeks. This review showed that conservative treatment in a closely monitored environment may be an appropriate first line treatment.

Meningovascular neurosyphilis is a common cause of stroke in young adults, particularly when HIV co-infection is present. Contemporary screening for neurosyphilis relies on invasive testing. High resolution vessel wall imaging (HR-VW) is an emerging non-invasive tool to detect intracranial vessel wall inflammation. We report a case of multifocal acute cerebral infarctions from meningovascular neurosyphillis in which HR-VWI was instrumental in leading to the etiological diagnosis. A 32-year-old man with history of untreated HIV and polysubstance abuse presented with sudden onset vertigo. CT angiogram of the head and neck showed non-dominant left extracranial vertebral artery occlusion in the V1 segment, and multifocal areas of stenoses in V2 through V4 segments. Non-contrast brain MRI demonstrated multiple small acute infarcts in the left cerebellum, left brachium pontis, medulla and occipital lobe. Rapid plasma reagin was reactive. 3D whole-brain HR-VWI revealed concentric vessel wall contrast enhancement in the left V4 segment, suggestive of inflammation. This HR-VWI finding prompted further investigation with cerebrospinal fluid analysis that revealed reactive fluorescent treponemal antibody absorption test. The patient received high-dose intravenous Penicillin G, was restarted on highly active antiretroviral therapy, and remained neurologically stable to-date. With high spatial resolution and signal-to-noise ratio, HR-VWI allows for visualization of vessel wall inflammation in co-morbid HIV and neurosyphilis.

Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder with recurrent non-arterial distribution stroke-like episodes (SLEs). A 17 yr old boy with MELAS (m.3243A>G tRNA^Leu(UUR)) presented with SLEs at ages 8 and 10 yrs. At 11 yrs, he suffered a third SLE involving left parietotemporal lobes with dense right hemiplegia and aphasia persistent for 1 week without improvement. On high dose IV L-Arginine (L-Arg) (0.5 g/kg/day divided TID) he had rapid recovery within 48 hours and was rapidly weaned. With emesis of oral L-Arg, his SLE recurred and he was again treated with high dose IV L-Arg with similar rapid recovery and discharged on a slow wean over 6 wks to 0.1 g/kg/day. On maintenance L-Arg he suffered only 2 SLEs at ages 13 and 16 yrs; both resolved rapidly with high dose IV L-Arg without recurrence during a slow wean to maintenance. His phenotype included seizures, ptosis, ophthalmoplegia, facial diplegia, sensorineural hearing loss, ataxia, myopathy, exercise intolerance, peripheral sensorimotor neuropathy, hypertrophic cardiomyopathy, hypertension, and failure to thrive. At 16 yrs he developed end-stage renal disease, due to MELAS, requiring hemodialysis and at 17 yrs he underwent cadaveric renal transplantation. His peri-operative protocol included strict maintenance of perfusion, oxygenation, normothermia, biochemical homeostasis and serum arginine concentrations during which time there were no neurologic decompensations. He was transitioned to oral L-citrulline maintenance therapy which maintained higher serum arginine concentrations with better tolerance. He had no SLEs or seizures in the ensuing 2 yrs.

Axicabtagene ciloleucel (AC) is an FDA-approved anti-CD19 autologous chimeric antigen receptor T-cell (CAR-T) therapy for refractory diffuse large B cell lymphoma (DLBCL). While its efficacy in DLBCL has been promising, neurotoxicity remains a significant concern. We present a case of a 22-year-old woman with chemotherapy-refractory DLBCL who exhibited Grade IV neurotoxicity in the setting of sepsis, after undergoing AC infusion. Despite prophylactic levetiracetam given per guidelines,^1,2 she experienced a precipitous mental status decline on post-infusion day 8 (D8) followed by hypoxic respiratory failure in the setting of clinical status epilepticus on D11 and nonconvulsive status epilepticus (NCSE) on D18. While neuroimaging was unremarkable, EEG demonstrated diffuse slowing and 2.5–3 Hz generalized periodic discharges consistent with NCSE. Seizures were initially refractory to lorazepam, increasing doses of levetiracetam, and phenobarbital, requiring a midazolam drip titrated to 50–70% burst suppression for resolution. Methylprednisolone and tocilizumab were used to treat neurotoxicity and cytokine release syndrome, respectively. Empiric antibiotics were used for sepsis. After cessation of sedatives on D19, mental status improved to near baseline. PET/CT just prior to discharge showed a complete response of the DLBCL (Deauville 3). She was discharged on D37 with no further seizure activity. Unfortunately, a 3-month interval PET/CT demonstrated disease progression which continued through salvage pembrolizumab eventually leading to death 1.2 years post-CAR-T infusion. This case illustrates the clinical management challenges of a complex and rare neurotoxic side effect of CAR-T cell therapy, namely NCSE following status epilepticus.

In late 2019, the novel coronavirus, SARS-CoV-2, and the disease it causes, COVID-19, was identified. Since then many different neurological manifestations of COVID-19 have been well reported. Movement abnormalities have been rarely described. We report here a critically ill patient with COVID-19 who developed generalized myoclonus during the recovery phase of the infection. Myoclonus was associated with cyclical fevers and decreased alertness. Movements were refractory to conventional anti-epileptic therapies. There was concern that myoclonus could be part of a post-infectious immune-mediated syndrome. The patient improved fully with a 4-day course of high-dose steroids. Our experience highlights a rare, generalized myoclonus syndrome associated with COVID-19 that may be immune-mediated and is responsive to treatment.

Acute necrotizing encephalopathy (ANE) is a rare and life-threatening disease. It is caused by a cytokine-mediated injury to the brain with characteristic hemorrhagic and edematous lesions involving the bilateral thalami, brainstem, and other subcortical structures. The disease is commonly associated with antecedent viral triggers such as influenza, parainfluenza, and more recently, SARS-CoV-2, with subsequent neurologic deterioration occurring within days to weeks. Here, we present a case of a pregnant adult woman who developed a hyperacute form of ANE, progressing to brain death within 36 hours of symptom onset. Her diagnosis was confirmed via brain imaging, CSF studies, and neurohistopathological analysis. This case highlights the importance of establishing an early diagnosis for this under-recognized disease, and also suggests an association between ANE and early pregnancy.

Invasive cryptococcal infection in a previously immunocompetent patient complicating coronavirus disease 2019 (COVID-19) pneumonia has not been described before. In this report, a 76-year-old woman survived a bout of respiratory failure from severe COVID-19 pneumonia, during which she received remdesivir, convalescent plasma, corticosteroids, and tocilizumab. Soon after discharge, she developed acute encephalopathy and multifocal ischemic strokes. CSF and blood cultures were positive for Cryptococcus neoformans. Cryptococcal meningoencephalitis should be considered in the differential diagnosis of encephalopathy in a patient with COVID-19. Treatment with high-dose steroids and tocilizumab may be predisposing factors.

Opsoclonus myoclonus syndrome (OMS) is a rare immune-mediated paraneoplastic or para/-post-infectious syndrome characterized by “dancing” eye movements, myoclonus, and ataxia. Neuropsychiatric symptoms have also been reported. Without treatment, OMS may progress to further neurological impairment and even death. Autoimmune attack of CNS structures in OMS is most commonly mediated by anti-Ri (also known as ANNA2) IgG antibodies, with additional findings implicating antibodies targeting various neurotransmitter receptors. Prompt immunotherapy and neoplasm treatment may result in improvement. We report a novel association of Contactin-Associated Protein-Like 2 (Caspr2) antibodies occurring in association with paraneoplastic OMS. While breast cancer and small cell lung cancer (SCLC) are more commonly associated with OMS among adults, we characterize a novel association between Caspr2 antibody in a patient with mixed non-small cell and small cell lung carcinoma.

Scrub typhus, an acute febrile infectious disease prevalent in the ‘tsutsugamushi triangle’, is a mite-born rickettsial zoonosis, caused by Orientia tsutsugamushi. The clinical presentation is protean and involves multiple organ systems of the body, including central and peripheral nervous systems. We report a 22-year-old previously healthy Indian woman who presented with clinical (confusion, excessive sleepiness, cognitive dysfunction and focal seizures) and neuroimaging features of limbic encephalitis. After exclusion of common infectious, autoimmune and paraneoplastic causes, she was diagnosed with scrub typhus associated encephalitis, which responded to doxycycline and azithromycin therapy.

A plethora of neurological manifestations are associated with the 2019 coronavirus infectious disease (COVID-19). We hereby report the first case of a patient infected with SARS-CoV-2 who acutely presented with autonomic dysfunction preceding the onset of complete clinical picture of Miller Fisher syndrome. She was finally diagnosed to be a case of anti-ganglioside antibody positive post-COVID-19 Miller Fisher syndrome with dysautonomia and treated with intravenous immunoglobulin with an excellent response. We also discuss the plausible pathogenic mechanisms of COVID-19 induced Miller Fisher syndrome and furnish a review of the post-COVID-19 Miller Fisher syndrome cases reported.

We report a case of a woman with a history of systemic lupus erythematosus who developed persistent ataxia and was diagnosis with lupus cerebellitis. Magnetic resonance imaging of the brain showed T2/FLAIR signal hyperintensity within the cerebellar vermis without mass effect. The patient’s condition improved with pulse IV methylprednisolone. This case highlights unique imaging findings within the cerebellum, our diagnostic and treatment regimen, and compares this case to previous literature on similar cases.

A 64-year-old man with a history of diabetes mellitus and end stage renal disease presented with a several day history of cognitive decline, reduced right eye visual acuity accompanied with a complete right ophthalmoplegia in keeping with orbital apex syndrome. Initial MRI was unremarkable other than mucosal thickening in the frontal sinuses. He continued to clinically decline and repeat MRI revealed an edematous right optic nerve and a lack of enhancement within the sinuses was suspicion for invasive fungal infection. Given his history of diabetes, he was started on anti-fungal treatment and taken for debridement but passed away several days later. This case illustrates the importance of the orbital apex syndrome as a localization. Mucormycosis should be considered in acute onset ophthalmoplegia particularly in patients with diabetes and diabetic ketoacidosis. Empiric anti-fungal therapy should be started early for suspected rhino-orbital cerebral mucormycosis, although mortality remains high despite treatment.

Neuromelioidosis is a severe tropical infection with high morbidity and mortality. Isolated myelitis is an extremely rare manifestation of melioidosis which may evade diagnosis. We report a 69-year-old diabetic male patient who presented with acute flaccid paraplegia and longitudinally extensive myelitis and no systemic symptoms. MRI of spinal cord showed lower dorsal cord and conus T2 hyperintensity and microabscesses with dural enhancement. The diagnosis was clinched with blood culture growing Burkholderia pseudomallei. He rapidly developed colitis, septicemia and multiorgan dysfunction and succumbed to the illness in spite of antibiotics and aggressive supportive care. The case highlights that melioidosis should be considered as a differential diagnosis of infectious myelitis, especially in the tropics. Presence of a neutrophilic blood and cerebrospinal fluid picture and microabscesses in spinal cord are important diagnostic clues. The outcome is dismal unless the diagnosis is considered early in the disease course and managed expeditiously with sensitive antibiotics.

Jamestown canyon virus (JCV) is an arbovirus and is an under-recognized cause of mosquito-borne viral encephalitis. In this report we present a patient who presented with focal neurological deficits. Patient was initially evaluated for stroke. However, leptomeningeal enhancement on MRI and CSF studies were concerning for viral encephalitis. Brain biopsy and CSF sample from surgical site was positive for JCV IgM antibodies. Patients presenting with concern for viral encephalitis in endemic areas should undergo antibody testing for JCV to guide appropriate treatment.

Trigeminal neuralgia associated with brainstem lesions is currently considered as a rare condition and only few patients have been reported so far in literature. Tohyama and colleagues recently proposed the nosological entity of trigeminal neuralgia associated with solitary pontine lesion, trying to categorize it as a new clinical syndrome on its own. Based on this description, trigeminal neuralgia associated with solitary pontine lesion patients have an identical clinical presentation compared to other patients with trigeminal neuralgia but have a solitary pontine lesion. The nature of the pontine lesion has been attributed to several etiologies, including ischemia, demyelination or previous pontine viral neuritis. In those patients with a putative demyelinating lesion, a definite diagnosis of multiple sclerosis cannot be made due to the lack of dissemination in space. Very little is known in relation to the cerebrospinal fluid characteristics of this population of patients.

We present a case of a 42-year-old man suffering of trigeminal neuralgia associated with solitary pontine lesion with a possible demyelinating etiology. The patient herein described had an atypical trigeminal neuralgia associated with a single pontine lesion. The MRI characteristics of the lesion, along with the presence of oligoclonal bands in the cerebrospinal fluid, suggested a demyelinating etiology. Trigeminal neuralgia associated with a solitary pontine lesion may be categorized as a possible manifestation of solitary sclerosis. Future research need to reveal which features can predict the risk of conversion to clinically defined multiple sclerosis and which treatments modify this risk.

Seizures and involuntary movements are relatively rare, but well-known neurological complications of non-ketotic hyperglycemia. While hemichorea-hemiballism secondary to diabetic striatopathy is increasingly being reported, unilateral caudate atrophy resulting from chronic vascular insufficiency/insult in a backdrop of poorly controlled diabetes mellitus is sparsely described in literature. We herein report a 75-year-old woman with poorly controlled diabetes mellitus who presented with concurrent epilepsia partialis continua involving left side of her face and hemichorea on the right side in the context of non-ketotic hyperglycemia. Neuroimaging revealed a space-occupying lesion suggestive of low-grade glioma in the right superior frontal cortex and left-sided caudate atrophy as well. Possibly, space-occupying lesion in motor cortex acted as an inciting factor for seizures and non-ketotic hyperglycemia further lowered the seizures threshold. On the other hand, atrophied left caudate had led to persistent choreiform movements secondary to chronic uncontrolled hyperglycemia. The simultaneous presence of acute and chronic neurological complications of diabetes mellitus makes this case unique. It also highlights the need for strict control of blood glucose and utility of appropriate neuroimaging to rapidly diagnose and prevent further complications.

Severe meningitis, especially basilar meningitis, can lead to hydrocephalus requiring external ventricular drain (EVD) placement. There are differences in cerebrospinal fluid (CSF) obtained from an EVD compared to a lumbar puncture (LP). Hence, it becomes difficult to compare LP and EVD samples for diagnosis and monitoring of meningitis. Recognizing these differences is important to properly treat and discontinue antibiotics. We report a case series of 6 patients with meningitis comparing EVD and LP CSF study analysis. In all 6 patients, CSF from LP was obtained before EVD placement by 1.7 days on average. Although corrected white blood cell (WBC) counts were elevated in CSF obtained from LP and EVD, the counts were significantly higher in LP CSF. Protein concentration in LP CSF was also significantly higher than EVD CSF. Glucose and red blood cells varied in both LP and EVD samples. Even though EVD CSF was obtained later in the clinical course than LP, slower circulation of CSF in lumbar space as compared to ventricles is likely the reason for a more sterile appearance of EVD CSF for the diagnosis of meningitis. It is important to recognize these differences as EVD CSF analysis for diagnosis of meningitis may lead to a missed diagnosis and false perception of significant improvement when monitoring response to treatment. One can consider repeating LP prior to discontinuation of antibiotics to properly determine the extent of improvement given EVD CSF sample appears more sterile in comparison. Larger studies are needed to confirm the above findings.

The artery of Davidoff and Schechter (ADS) is the only meningeal branch of the posterior cerebral artery (PCA), supplying the medial tentorial margin and posterior portions of the falx. Given its small size, it is rarely identified on angiographic studies, unless enlarged in pathologies such as dural arteriovenous fistulas (DAVFs) or vascularized masses. This artery was first described by Wollschlaeger and Wollschlaeger in 1965, and to date, only a few reports have described its significance. The objective of this study is to report our experience with the ADS in dural fistulas from 2 tertiary medical centers and to emphasize the importance of recognizing this artery during angiographic examination of vascular tentorial and posterior fossa lesions. To our knowledge, this report demonstrates the largest angiographic case series published to date, recognizing a total of 7 patients with ADS arising secondary to a posterior fossa or tentorial DAVF and one of the largest reported series of DAVFs supplied by the ADS treated by endovascular and surgical techniques. Our cases validate the importance of prompt identification of the ADS for the diagnosis as well as endovascular treatment of vascular malformations in the posterior fossa and tentorial region.

This report explores the case of a 49-year-old African American male with a six-month history of multifocal neurological deficits who presented to an outside hospital after a generalized seizure. Patient was transferred to our tertiary medical center after brain imaging showed multiple bilateral supratentorial intraparenchymal hemorrhages (IPH). A brain biopsy confirmed parenchymal and perivascular non-caseating granulomas with vasculitis. The patient was definitively diagnosed with neurosarcoidosis (NS) and his condition improved with high dose corticosteroids and additional immunosuppressive therapies. Intracranial hemorrhage in the setting of NS is extremely rare, with fewer than thirty documented cases; however, this is likely an underestimation of its true prevalence. This case illustrates the difficulty in diagnosis as many other etiologies of IPH must be considered. Additionally, the clinical course and manifestations of NS is often quite variable. The uniqueness of this case lies in the rapid progression from seemingly incidental microhemorrhages to multiple large IPHs over two months. While the cause of this progression is not immediately apparent, a possible cause may be inadequate initial treatment due to delayed diagnosis. Our case demonstrates the importance of early recognition and initiation of immunosuppressive therapy, potentially leading to dramatic clinical improvement, as seen in this patient.

A 67-year-old woman was admitted to our hospital for progressive weakness, dysphagia, muscle pain, and weight loss. Here we detail the clinical problem solving involved in diagnosing and treating her immune-mediated necrotizing myopathy caused by anti-HMGCoA reductase autoantibodies. Interestingly, this diagnosis coincided with discovery of a gastrointestinal stromal tumor (GIST) and positivity for anti-nuclear matrix protein (anti-NXP2), another myositis specific autoantibody.

We present a case of new onset bilateral lower extremity weakness, paresthesia, urinary retention and bowel incontinence in a 51-year-old man. He had a complicated history of acute myelogenous leukemia with known central nervous system (CNS) and leptomeningeal involvement status post allogenic stem cell transplant complicated by chronic graft versus host disease (GVHD). We review the differential diagnosis as the physical exam and diagnostic results evolved. We also provide a review of the relevant literature supporting our favored diagnosis, as well as other competing diagnoses in this complicated case. The ultimate differential diagnosis included viral myelitis, treatment-related myelopathies, and CNS GVHD. The case provides a sobering reminder that even with an appropriate diagnostic workup, some cases remain refractory to therapeutic efforts. It also underscores the importance of a sensitive neurologic exam, given the significant clinico-radiological delay, and reviews the complex differential diagnosis for myelopathy.

We present a case of a healthy 62-year-old woman who developed recurrent seizures preceded by subacute cognitive slowing, ataxia, night sweats, and weight loss. She was found to have cytopenias, multifocal T2/FLAIR hyperintensities on magnetic resonance imaging (MRI), and magnetic susceptibility artifact lesions on susceptibility weighted imaging (SWI). Her symptoms, imaging and laboratory abnormalities all improved with high-doses of steroids and intravenous immunoglobulin (IVIG). But recurred several weeks after completing treatment. Despite extensive work-up, she required multiple hospitalizations and repeat diagnostic studies to arrive at a diagnosis. With an expert discussant in hematology and oncology, we review the differential diagnosis and stepwise approach of unexplained neuro-inflammatory syndromes with cytopenias and systemic symptoms. Our case highlights how time, empiric treatment response, and repeated diagnostic studies refine differential diagnoses and subsequent evaluation. After revealing the diagnosis, we discuss the heterogenous clinical manifestations of this disease process.