Neurological manifestations as primary presentation of COVID-19 in hospitalized patients.

OBJECTIVE: To characterize patients with coronavirus disease 2019 (COVID-19) who presented primarily with neurologic symptoms without typical COVID-19 symptoms of fever, cough, and dyspnea. METHODS: We retrospectively identified COVID-19-positive patients 18 years and older that had neurology symptoms on presentation requiring neurology consultation between March 14, 2020 and May 18, 2020. The patients were then classified into those with typical COVID-19 symptoms and those without. Demographic, clinical symptoms, laboratory result, and clinical outcomes were collected. RESULTS: Out of 282 patients who had neurology consult during this period, we identified 56 (mean age 69.2 years, 57% women) who tested COVID-19-positive and had neurologic symptoms on initial presentation. Of these, 23 patients (mean age 65.2 years, 52% women) had no typical COVID-19 symptoms while 33 did (mean age 72.2 years, 60% woman). In both groups, impaired consciousness was the most common initial neurologic symptom, followed by stroke, unsteady gait, headache, seizure, syncopal event, acute vision changes, and intracranial hemorrhage. Out of the 23 patients without typical COVID-19 symptoms on presentation, 10 went on to develop typical symptoms with 8 needing supplemental oxygen and one requiring mechanical ventilation. CONCLUSION: Patients who have COVID-19 can present with serious neurologic symptoms such as impaired consciousness and stroke even without typical COVID-19 symptoms. Those without typical COVID-19 symptoms can later develop typical symptoms severe enough to need respiratory support.

Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings.

BACKGROUND: Celiac disease (CD) is increasingly recognized in North America and is associated with a peripheral neuropathy. OBJECTIVE: To report the clinical characteristics and skin biopsy results in patients with CD and small-fiber neuropathy symptoms. DESIGN: Case series. SETTING: Academic peripheral neuropathy clinic. PATIENTS: Eight patients with CD and neuropathy symptoms. Intervention Three-millimeter punch biopsy using the panaxonal marker protein gene product 9.5 to assess epidermal nerve fiber (ENF) density and a gluten-free diet. MAIN OUTCOME MEASURE: Clinical data and ENF density. RESULTS: All patients had asymmetric numbness and paresthesias. Three had more prominent involvement of hands than feet, and 3 had facial numbness. Celiac disease was diagnosed in 5 after their neuropathy began. The following serum antibody levels were elevated: tissue transglutaminase (n = 6), IgA gliadin (n = 4), and IgG gliadin (n = 7). Results of nerve conduction studies were normal in 7 patients. One patient had mildly reduced sural amplitudes. The ENF density was reduced in 5 patients. The ENF density was at the low limit of the normal range in 3 additional patients, 2 of whom had morphologic changes in axons. Three patients had decreased ENF density at the thigh or forearm, which was more severe than at the distal leg, compatible with a non-length-dependent process. Four reported improvement with a gluten-free diet. One had no improvement after 4 months. Symptoms developed in 2 while receiving a gluten-free diet. CONCLUSIONS: Patients with CD may have a neuropathy involving small fibers, demonstrated by results of skin biopsy. The pattern of symptoms, with frequent facial involvement and a non-length-dependent pattern on skin biopsy findings, suggests a sensory ganglionopathy or an immune-mediated neuropathy. Improvement of symptoms in some patients after initiating a gluten-free diet warrants further study.

Characterization of neuropathies associated with elevated IgM serum levels.

BACKGROUND: In contrast to the IgM monoclonal gammopathies the neuropathy associated with polyclonal IgM gammopathy has not been well characterized. OBJECTIVE: To characterize the neuropathy in patients with elevated serum IgM. DESIGN: Retrospective review. SETTING: Academically based neuropathy center. PATIENTS: 45 patients with elevated quantitative immunoglobulin M were identified. MAIN OUTCOME MEASURES: Patients are described with regard to clinical phenotype, electrodiagnostic features of demyelination or focality, presence of IgM monoclonal gammopathy, and presence of autoantibody activity. RESULTS: Elevated IgM levels occurred in 45 (11.5%) of 391 patients. Of these, 24 (53%) had polyclonal gammopathy and 21 (47%) had an IgM monoclonal gammopathy. Anti-nerve antibodies occurred in 14/21 (67%) of patients with monoclonal gammopathy, as compared to 1/24 (4%) with polyclonal gammopathy. Clinically, most patients in all groups had a predominantly large fiber sensory neuropathy. Thirty patients underwent electrodiagnostic testing. Of these, 22/30 (73%) fulfilled at least one published criteria for CIDP, including 92% of the monoclonal gammopathy patients and 59% of the polyclonal gammopathy patients. Fifteen of the 30 patients had evidence of focality or multifocality, with 14 of these 15 showing evidence of demyelination. CONCLUSIONS: Monoclonal and polyclonal IgM patients have similar distributions of neuropathy phenotypes. Neuropathy in association with elevated serum IgM, with or without monoclonal gammopathy or autoantibody activity, is more likely to be demyelinating or multifocal. Serum quantitative IgM level and immunofixation in neuropathy patients may aid in identification of an immune mediated or a demyelinating component.

Multifocal acquired sensory and motor neuropathy: electrodiagnostic features.

The electrodiagnostic studies of 13 consecutive patients with multifocal sensory and motor neuropathy of unknown etiology were reviewed to determine whether they exhibit features of demyelination or axonal degeneration. The type and frequency of demyelinating features, fulfillment of electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP), and response to immunotherapy were noted. Of 13 patients, 11 had at least one electrodiagnostic feature of demyelination at presentation and 2 had none. Seventeen percent to 77% of the patients fulfilled at least one of the published electrodiagnostic CIDP criteria, depending on the criteria used, but the number of demyelinating features per patient was less than reported for unselected patients with CIDP. Patients with multifocal sensory and motor neuropathy had a similar percentage of nerves with partial conduction block or F-wave prolongation as reported for unselected CIDP, but a smaller percentage of nerves exhibiting prolonged distal compound muscle action potential duration, distal latency prolongation or slowed conduction velocities. All treated patients, including 2 who did not meet any CIDP criteria, had at least a moderate response to immunotherapy. The results indicate that a large majority of, but not all, patients with idiopathic multifocal sensory and motor neuropathies exhibit electrodiagnostic features of demyelination, although fewer than seen in classic CIDP.

Sensory CIDP presenting as cryptogenic sensory polyneuropathy.

The objective of this study was to report that patients with chronic inflammatory demyelinating polyneuropathy (CIDP) can present with a clinical picture of cryptogenic sensory neuropathy. Patients with distal sensory neuropathy and electrodiagnostic studies that are minimally abnormal or consistent with an axonal pathology are usually diagnosed as having cryptogenic sensory neuropathy if no cause for neuropathy can be found. Some of these patients, however, may have sensory CIDP. We reviewed the records of eight patients with CIDP, diagnosed by sural nerve biopsy, who presented with sensory neuropathy and electrodiagnostic studies that were minimally abnormal or revealed changes consistent with axonal neuropathy. All patients reported distal numbness and paresthesias and, on examination, had predominantly large fiber distal sensory loss and normal muscle strength. In most patients, deep tendon reflexes were reduced or absent. Sural nerve biopsies in all patients were consistent with chronic myelinopathy, with quantitative teased fiber analysis revealing segmental remyelination in 13-40% of the fibers. The four patients who received IVIg therapy had improved sensation and gait. Of the remaining four patients, one is being followed, one had spontaneous remission, one was lost to follow-up, and one, with contraindications to therapy, reported disease progression. Sensory CIDP may present as cryptogenic sensory polyneuropathy with normal or axonal electrophysiologic features. Sural nerve biopsy should be considered in patients with progressive, predominantly large fiber sensory neuropathy of otherwise unknown etiology, as they may have sensory CIDP that responds to therapy.

Comparison of electrodiagnostic abnormalities and criteria in a cohort of patients with chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) are research oriented favoring specificity over sensitivity. Application of such criteria in clinical practice may miss the diagnosis in potentially treatable patients. OBJECTIVES: To analyze the electrophysiologic abnormalities in a cohort of patients with clinically defined CIDP, to compare these data with published electrodiagnostic criteria, and to identify a set of abnormalities that is shared by all patients with CIDP. DESIGN: Retrospective medical record review. SETTING: Academically based neuromuscular clinic. Patients Fifteen patients with clinically diagnosed relapsing sensorimotor CIDP. INTERVENTIONS: Administration of intravenous immunoglobulin or prednisone. MAIN OUTCOME MEASURES: Electrodiagnostic studies. RESULTS: All patients had electrodiagnostic abnormalities in at least 3 nerves with possible partial conduction block or demyelinating range abnormalities in at least 1 nerve. The diagnostic sensitivities of 5 published CIDP criteria were as follows: the Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force (40%), Saperstein et al (47%), Nicolas et al (53%), Hughes et al for the Inflammatory Neuropathy Cause and Treatment Group (60%), and Thaisetthawatkul et al (70%). CONCLUSIONS: Current electrodiagnostic criteria for CIDP are insensitive and may fail to diagnose the condition in a substantial number of patients. More inclusive criteria that allow identification of patients in routine clinical practice are needed.

Quantitative sensory testing: high sensitivity in small fiber neuropathy with normal NCS/EMG.

We evaluated the diagnostic sensitivity of quantitative sensory testing (QST), using the CASE IV system, in 14 patients with clinically diagnosed small-fiber neuropathy and normal traditional electrodiagnostic studies. All patients had at least 1 abnormal threshold, 13 patients had abnormal heat-pain thresholds, 8 had abnormal cold thresholds, and 7 had abnormal vibration thresholds. QST is therefore highly effective in documenting dysfunction in small fiber neuropathy patients.