Cerebrospinal Fluid Anti-Neuronal Autoantibodies in COVID-19-Associated Limbic Encephalitis with Acute Cerebellar Ataxia and Myoclonus Syndrome: Case Report and Literature Review.

Since the outbreak of coronavirus (COVID-19) in 2019, various rare movement disorders and cognitive changes have been recognized as potential neurological complications. The early treatment of some of these allows rapid recovery; therefore, we must diagnose these manifestations in a timely way. We describe the case of a 76-year-old man infected with severe acute respiratory syndrome coronavirus-2 who presented with confusion and hallucinations and was admitted to our hospital 14 days after the onset of symptoms. One day later, he developed generalized myoclonus, dysarthria and ataxia, and tonic clonic seizures and was admitted to the intensive care unit. A diagnosis of COVID-19-associated autoimmune encephalitis with characteristics of limbic encephalitis and immune-mediated acute cerebellar ataxia and myoclonus syndrome was supported by alterations in the limbic system shown in magnetic resonance imaging, lateralized discharges shown in electroencephalography, a slightly elevated protein level in the cerebrospinal fluid (CSF), and indirect immunofluorescence in the CSF with autoantibody binding to anatomical structures of the cerebellum and hippocampus. The patient improved with 2 weeks of corticosteroid treatment and four sessions of plasmapheresis. Our current case study describes a rare case of COVID-19-related limbic encephalitis with immune-mediated acute cerebellar ataxia and myoclonus syndrome (ACAM syndrome) and strengthens the need for tissue-based assays (TBAs) to screen the serum and/or CSF of patients highly suspected to have autoimmune encephalitis. We believe that the timely diagnosis and targeted aggressive immunotherapy were mainly responsible for the patient's total recovery.

Co-occurrence between hereditary angioedema and multiple sclerosis: Therapeutic management of both diseases with fingolimod.

BACKGROUND: Hereditary angioedema (HAE) related to C1 esterase-inhibitor deficiency activates the classic complement pathway and results to edematous crises. Although HAE is usually associated with multiple immunoregulatory disorders, neurologic manifestations are rare. CASE REPORT: We report on the case study of a 33-year-old man diagnosed with HAE (SERPIN1G gene mutation) and multiple sclerosis (MS), followed up for at least 6 years. After a first clinical attack of HEA with scrotal edema, MS disease exacerbation was observed. Treatment with glatiramer acetate could not prevent either MS or HAE clinical attacks with recurrent exacerbations been observed. Remission of MS and significant amelioration of HAE attacks were achieved under fingolimod treatment. CONCLUSIONS: Herein we provide long term evaluation of an extremely rare case of concomitant existence of HAE and MS and present the effects of MS current disease-modifying therapies in HAE attacks. Our case highlights the possible effect of fingolimod in immunoregulatory-mechanisms implicated in both diseases.

IgG4-related autoimmune manifestations in Alemtuzumab-treated multiple sclerosis patients.

We aimed to determine whether Alemtuzumab-induced immune reconstitution affects immunoglobulin and complement levels in the serum of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. IgG4-levels were increased 24-months after treatment initiation compared to baseline levels in twenty-nine patients. Alemtuzumab-treated patients with the highest IgG4-levels were more prone to thyroid-related autoimmune manifestations and specific autoimmune adverse events such as Crohn's disease, Graves' disease, and hemolytic anemia. Compared to baseline, total IgG-levels showed a trend towards reduced levels following two-courses of Alemtuzumab, but no significant change of C3 and/or C4-levels was observed. In conclusion, monitoring of IgG4-levels can serve as a marker for secondary autoimmunity risk in multiple sclerosis patients treated with Alemtuzumab.

Clinico-radiologic features and therapeutic strategies in tumefactive demyelination: a retrospective analysis of 50 consecutive cases.

AIMS: Our goal was to expand the spectrum of clinico-radiologic characteristics and the possible therapeutic choices in patients with tumefactive demyelinating lesions (TDLs). METHODS: A retrospective analysis of 50 patients with at least one TDL was performed at an academic neurology center (2008-2020). RESULTS: Our cohort comprised mostly women (33/50) with a mean age of 38 years at TDL onset. The mean follow-up time was 76 months. The mean Expanded Disability Status Scale score at TDL onset and at the latest neurological evaluation was 3.7 and 2.3, respectively. We subcategorized the patients into seven groups based mainly on the clinical/radiological findings and disease course. Group A included patients presenting with a Marburg-like TDL (n = 4). Groups B and C comprised patients presenting with monophasic (n = 7) and recurrent TDLs (n = 12), respectively. Multiple sclerosis (MS) patients who subsequently developed TDL (n = 16) during the disease course were categorized as Group D. Group E comprised patients who initially presented with TDL and subsequently developed a classical relapsing-remitting MS without further evidence of TDL (n = 5). Groups F (n = 2) and G (n = 4) involved MS patients who developed TDL during drug initiation (natalizumab, fingolimod) and cessation (interferon, fingolimod), respectively. Regarding long-term treatments applied after corticosteroid administration in the acute phase, B-cell-directed therapies were shown to be highly effective especially in cases with recurrent TDLs. Cyclophosphamide was spared for more aggressive disease indicated by a poor response to corticosteroids and plasma exchange failure. CONCLUSION: Tumefactive central nervous system demyelination is an heterogenous disease; its stratification into distinct groups according to different phenotypes can establish more efficient treatment strategies, thus improving clinical outcomes in the future.

Lentiform fork sign in a patient with systemic lupus erythematosus.

The "lentiform fork sign" is a rare MRI sign which affects the posterior limb of the internal capsule, the external capsule, and extends posteriorly to form a fork-like appearance. It has been reported exclusively in disorders with metabolic acidosis, such as uremic encephalopathy, mitochondrial disorders, methanol/ethylene glycol intoxication, etc. It is considered to represent vasogenic edema and is often reversible. We describe a 73-year old female with a 2-month history of rapidly deteriorating imbalance, bradykinesia, confusion, and disorientation. At examination, she was encephalopathic. She had a pyramidal and rigid-akinetic parkinsonian syndrome, with signs of polyneuropathy. MRI revealed the "lentiform fork sign". She exhibited a high ANA titer, positive anti-dsDNA, anti-ENA, and anti-ß2GPI-IgM antibodies, as well as positive cerebrospinal fluid IgG and albumin indices. No metabolic acidosis was recorded. A diagnosis of systemic lupus erythematosus (SLE) was established. She was treated initially with methylprednisolone, followed by hydroxychloroquine, with complete remission of her symptoms and disappearance of the "lentiform fork sign". We present a case of a patient with SLE, harboring the "lentiform fork sign", in the absence of metabolic acidosis. Differential diagnosis of the "lentiform fork sign" should be expanded to include autoimmune disorders, even in the absence of metabolic acidosis.

Recurrent Fulminant Tumefactive Demyelination With Marburg-Like Features and Atypical Presentation: Therapeutic Dilemmas and Review of Literature.

Atypical forms of demyelinating diseases with tumor-like lesions and aggressive course represent a diagnostic and therapeutic challenge for neurologists. Herein, we describe a 50-year-old woman presenting with subacute onset of left hemiparesis, memory difficulties and headache. Brain MRI revealed a tumefactive right frontal-parietal lesion with perilesional edema, mass effect and homogenous post-contrast enhancement, along with other small atypical lesions in the white-matter. Brain biopsy of cerebral lesion ruled out lymphoma or any other neoplastic process and patient placed on corticosteroids with complete clinical/radiological remission. Two years after disease initiation, there was disease exacerbation with reappearance of the tumor-like mass. The patient initially responded to high doses of corticosteroids but soon became resistant. Plasma-exchange sessions were not able to limit disease burden. Resistance to therapeutic efforts led to a second biopsy that showed perivascular demyelination, predominantly consisting of macrophages, with a small number of T and B lymphocytes, and the presence of reactive astrocytes, typical of Creutzfeldt-Peters cells. The patient received high doses of cyclophosphamide with substantial clinical/radiological response but relapsed after 7-intensive cycles. She received 4-weekly doses of rituximab with disease exacerbation and brainstem involvement. She eventually died with complicated pneumonia. We present a very rare case of recurrent tumefactive demyelinating lesions, with atypical tumor-like characteristics, with initial response to corticosteroids and cyclophosphamide, but subsequent development of drug-resistance and unexpected exacerbation upon rituximab administration. Our clinical case raises therapeutic dilemmas and points to the need for immediate and appropriate immunosuppression in difficult to treat tumefactive CNS lesions with Marburg-like features.

Greece reports prototype intervention with first peripherally inserted central catheter: case report and literature review.

Placement of peripherally inserted central catheters (PICCs), definitely offers a clear advantage over any other method regarding central venous catheterization. Its ultrasonographic orientation enhances significantly its accuracy, safety and efficacy, making this method extremely comfortable for the patient who can continue his or her therapy even in an outpatient basis. We present the first reported case of a PICCS insertion in Greece, which has been performed by a university-degree nurse. The aim of this review of literature was to present the evolution in nursing practice in Greece. A PICC was inserted in a 77-year-old male patient suffering from a recent chemical pneumonia with a history of Alzheimer's disease. A description of all the technical details of this insertion is reported, focusing on the pros and cons of the method and a thorough review of the history and advances in central venous catheterization throughout the years is also presented. PICCs provide long-term intravenous access and facilitate the delivery of extended antibiotic therapy, chemotherapy and total parenteral nutrition. We strongly believe that PICCs are the safest and most effective method of peripherally inserted central venous catheterization. Larger series are necessary to prove the above hypothesis, and they are under construction by our team.

Gabapentin monotherapy for the treatment of chemotherapy-induced neuropathic pain: a pilot study.

OBJECTIVE: This study was conducted to investigate the efficacy and safety of gabapentin monotherapy in the management of chemotherapy-induced neuropathic pain. PATIENTS: Seventy-five cancer patients who had previously received chemotherapy, and had experienced at least one symptom of neuropathic pain were included in the intervention group. They received a fixed low-dose of gabapentin (800 mg/day). The control group consisted of 35 cancer patients with similar treatment history and symptomatology, who refused treatment with gabapentin and, therefore, received a fixed-dose combination of naproxen and codeine/paracetamol. OUTCOME MEASURES: Patients were grouped in three categories according to the severity of their neuropathic symptoms at baseline: mild, moderate, and severe. Analgesic efficacy of the study drug was assessed by means of a patient-answered questionnaire. Four stages of analgesic response were established: complete, partial, minor, and no response. RESULTS: All patients completed the study and were evaluable. In the intervention arm, gabapentin led to a complete response in 25.3% of patients (19/75), partial response in 44% (33/75), minor response in 25.3% (19/75), and no response in 5.3% (4/75). The response to gabapentin correlated with the severity of the underlying neurotoxicity. Approximately 25% of patients receiving gabapentin experienced mild somnolence, but none discontinued it. In the control group, none experienced complete response (0/35), while partial, minor, and no response were observed in 5.7% (2/35), 45.7% (16/35), and 48.6% (17/35), respectively. Compared with the control group, gabapentin therapy led to a statistically significant better response in patients of each baseline neurotoxicity group. CONCLUSIONS: Gabapentin monotherapy seems to be well tolerated and useful for the management of chemotherapy-induced neuropathic pain.

Analgesic activity of high-dose intravenous calcitonin in cancer patients with bone metastases.

We undertook a prospective, nonrandomized study with the objective to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain secondary to bone metastases. Our study population consisted of 45 cancer patients with bone metastases (26 men) with a mean age of 64 years (range, 48-70) who had completed chemotherapy, hormonal therapy and radiation therapy at least 30 days prior to enrollment in the study, and had intractable pain despite the use of common analgesics (acetaminophen, nonsteroidal anti-inflammatory agents, opioids) and bisphosphonates. The study medication was a 300-IU dose of sCT administered intravenously daily for 5 consecutive days and repeated every two weeks until no response was noticeable. The analgesic efficacy of sCT was evaluated by means of Huskisson's visual analogue scale and Keele's pain scale; the daily consumption of analgesic drugs and performance status were also monitored. None of the patients managed to completely discontinue the use of other analgesics, but 5 patients (11% of the total number) had an analgesic response that lasted 4 weeks and less than 5% of the patients continued to respond for 6 weeks. No significant side effects were observed. Our data show that intravenous calcitonin administered in a relatively high dose has a very limited therapeutic potential as an adjuvant analgesic for a short period of time in selected cancer patients with bone metastases.

Decreased prevalence of mixed cryoglobulinemia in the HAART era among HIV-positive, HCV-negative patients.

There is an established association between human immunodeficiency virus (HIV) infection and mixed cryoglobulinemia, as demonstrated in studies mostly conducted before the introduction of highly active antiretroviral therapy (HAART). To assess the impact of the latter on the cryoglobulinemic status in patients with HIV infection, 133 consecutive, unselected HIV-positive patients, from which only 8 (6%) had co-infection with hepatitis C virus (HCV), were evaluated for the presence of cryoglobulins, according to whether they received or not antiretroviral therapy (ART). Patients shown to be cryoglobulin-positive in a previous study were assessed prospectively, after introducing HAART. Cryoglobulinemia was found in 10 (7.5%) of 133 patients:4 (3.9%) of 101 patients receiving ART versus 6 (18.8%) of 32 patients not receiving ART (P = 0.013). When HCV-positive patients were excluded from the analysis, the correlation between cryoglobulinemia and ART remained significant (P = 0.019). Among 11 previously detected cryoglobulin-positive patients, 8 became cryoglobulin-negative after receiving HAART for a mean period of 6.5 years (P = 0.039). Thus, ART seems to decrease the prevalence of cryoglobulinemia in HIV-infected, HCV-negative patients, a finding which provides indirect evidence of the etiologic role of HIV in the pathogenesis of cryoglobulins.

Intramedullary spinal cord metastases in a patient with small-cell lung cancer.

We present the case of a 60-year-old male smoker with gait disturbance, lower limb sensory disturbance, and urinary difficulties of subacute onset and progressive course. He had been diagnosed 10 months earlier with limited stage small-cell lung cancer, had received chemotherapy, thoracic radiotherapy, and prophylactic cranial irradiation, and was in remission on follow-up. Examination revealed bilateral pyramidal tract signs, a T9 sensory level, and loss of vibration and position sense in the lower limbs. Gadolinium-enhanced MRI of the cervical and thoracic spinal cord revealed two enhancing intramedullary lesions consistent with metastases. Intramedullary metastases are exceedingly rare, accounting for only 3.4-6% of myelopathies in cancer patients, and they usually coexist with brain or leptomeningeal metastases. The presence of multiple metastases is even rarer, with two lesions found in only 10% of patients with intramedullary disease.

Effect of percutaneous endoscopic gastrostomy on gastro-esophageal reflux in mechanically-ventilated patients.

AIM: To investigate the effect of percutaneous endoscopic gastrostomy (PEG) on gastroesophageal reflux (GER) in mechanically-ventilated patients. METHODS: In a prospective, randomized, controlled study 36 patients with recurrent or persistent ventilator-associated pneumonia (VAP) and GER > 6% were divided into PEG group (n = 16) or non-PEG group (n = 20). Another 11 ventilated patients without reflux (GER < 3%) served as control group. Esophageal pH-metry was performed by the "pull through" method at baseline, 2 and 7 d after PEG. Patients were strictly followed up for semi-recumbent position and control of gastric nutrient residue. RESULTS: A significant decrease of median (range) reflux was observed in PEG group from 7.8 (6.2 - 15.6) at baseline to 2.7 (0 - 10.4) on d 7 post-gastrostomy (P < 0.01), while the reflux increased from 9 (6.2 - 22) to 10.8 (6.3 - 36.6) (P < 0.01) in non-PEG group. A significant correlation between GER (%) and the stay of nasogastric tube was detected (r = 0.56, P < 0.01). CONCLUSION: Gastrostomy when combined with semi-recumbent position and absence of nutrient gastric residue reduces the gastroesophageal reflux in ventilated patients.