TREX-1 related Aicardi-Goutières syndrome improved by Janus kinase inhibitor.

Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy classically characterized by early onset of severe neurologic injury with basal ganglia calcifications, white matter abnormalities, and progressive cerebral atrophy, along with lymphocytosis and raised interferon alpha (INFα) in the cerebrospinal fluid (CSF). Here, we report a 31/2 year-old patient born with prenatal onset AGS, first manifesting as intra-uterine growth retardation. Cranial ultrasonography and cerebral MRI revealed ventriculomegaly and periventricular and basal ganglia calcifications, along with cerebral atrophy. Perinatal infections and known metabolic disorders were excluded. Both CSF lymphocytosis and raised INFα were present. Molecular analysis disclosed two already described compound heterozygous pathogenic variants in TREX1 (c. 309dup, p.(Thr104Hisfs*53) and c. 506G > A, p.(Arg169His)). The evolution was marked by severe global developmental delay with progressive microcephaly. Promptly, the patient developed irritability, quadri-paretic dyskinetic movements, and subsequently tonic seizures. Sensorineural hearing loss was detected as well as glaucoma. Initially, he was symptomatically treated with trihexyphenidyl followed by levetiracetam and topiramate. At age 22 months, baricitinib (0.4 mg/kg/day) was introduced, leading to normal serum INFα levels. Clinically, dyskinetic movements significantly decreased as well as irritability and sleep disturbance. We confirmed that baricitinib was a useful treatment with no major side effect.

Acute confusional state in HaNDL syndrome.

OBJECTIVE: To assess epidemiological, clinical and neuroimaging features of acute confusional state in the Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) syndrome. BACKGROUND: HaNDL is an increasingly recognized syndrome in which migraine-like headache episodes accompanied by hemiparaesthesia and/or hemiparesis and/or dysphasia are associated to CSF lymphocytic pleocytosis. The International Classification of Headache Disorders (ICHD-3) includes HaNDL syndrome in group 7 "headache attributed to non-vascular intracranial disorder" code 7.3.5, and lists the HaNDL-associated signs/symptoms that may be found less frequently. Confusional state is not mentioned in the 7.3.5-ICHD-3 "notes" or "comments" section as part of the HaNDL neurological spectrum. Moreover, the acute confusional state pathogenesis in HaNDL syndrome remains still uncertain and debated. METHODS: Here, we report a 32-year-old male who complained episodes of migraine-like headache and left hemiparaesthesia complicated by confusional state which led to discovering CSF lymphocytosis. Since other workup to determine the cause of his symptoms was otherwise negative, he was diagnosed as having HaNDL syndrome. We also ascertained and reviewed all available reports of HaNDL to assess the significance of confusional state in this syndrome. RESULTS: The search yielded 159 HaNDL cases among single reports and small/large series. Out of 159 patients who fulfilled the inclusion criteria for HaNDL according to the current ICHD at the time of diagnosis, 41 (25.7%) presented with acute confusional state. Among 41 HaNDL patients with confusional state, 16 (66.6%) out of 24 who underwent spinal tap had increased opening pressure. CONCLUSION: We propose that a mention of acute confusional state may be included in the "comments" section of "7.3.5-syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL)," when ICHD-3 diagnostic criteria will be updated. Moreover, we speculate that intracranial hypertension may play a role in the pathogenesis of the acute confusional state associated to HaNDL syndrome. Larger case series are needed to evaluate this hypothesis.

Prognostic value of acute cerebrospinal fluid abnormalities in antibody-positive autoimmune encephalitis.

OBJECTIVE: To examine the prognostic value of CSF abnormalities in seropositive autoimmune encephalitis (AE). METHODS: We retrospectively studied 57 cases of seropositive AE. Primary outcomes were mortality and modified Rankin Scale, while secondary outcomes were first line treatment failure, ICU admission and relapse. Regression analysis was performed. RESULTS: CSF white cell count (WCC) was higher in the NMDAR group, while elevated protein was more common amongst other subtypes. We found an association between WCC >5 cells/mm3 and treatment failure (OR 16.0, p = 0.006)), and between WCC >20 cells/mm3 and ICU admission (OR 19.3, p = 0.026). CONCLUSIONS: Different subsets of AE have characteristic CSF abnormalities, which may aid recognition during early evaluation. CSF WCC had prognostic significance in our study.

Discrepancy between ventricular and lumbar CSF in chronic meningitis.

Meningitis patient can present with various manifestation including hydrocephalus due to multiple reason. Diagnosis of meningitis mainly rely on CSF analysis which is usually obtained from lumbar puncture. In case of hydrocephalus CSF can be obtain from ventricles during VP shunt operation. Sometimes ventricular CSF can be normal in meningitis patient while lumbar CSF shows abnormality. Possible mechanisms behind this phenomenon are discussed here. Patients who present with hydrocephalus and have normal Ventricular CSF should investigated with lumbar CSF analysis in a view of delay in diagnosis and treatment.

To handle the HaNDL syndrome through a case: The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis.

The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare entity. This disease has been related to migrainous headaches. It is a benign, self-limited disorder, which is characterized by fluctuating neurological symptoms and cerebrospinal fluid lymphocytosis. We describe a case of a 47 years old man with acute onset of headache and aphasia. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis (25 cells/µl, 100% lymphocytes). Electroencephalogram showed moderate slow rhythm in the left hemisphere, with temporoparietal predominance, and without epileptiform activity. His blood tests as well as magnetic resonance imaging (MRI) results were normal. With the diagnosis of HaNDL syndrome the patient was accepted in the Department of Neurology and discharged with full recovery.

Post-Epstein-Barr Virus Acute Cerebellitis in an Adult.

BACKGROUND Acute cerebellitis in adults is a rare disease. The etiology is unknown but postulated to be due to primary infection or para-infection. Different presentations have been reported, which complicates the diagnosis process. CASE REPORT We report the case of a young man who presented with headache, vomiting, and vertigo. He was found to have ataxia and cerebellar signs, bradycardia magnetic resonance imaging (MRI) of the brain showed acute cerebellitis, and cerebrospinal fluid (CSF) studies showed lymphocytosis. Further investigations showed the presence of Epstein-Barr virus (EBV) immunoglobulin M (IgM) and IgG. His symptoms resolved completely with corticosteroid and antiviral treatments. CONCLUSIONS Acute cerebellitis can present in various ways. Bradycardia, along with neurological deficits, should raise the suspicion of acute cerebellitis.

[HaNDL syndrome in a 12-year-old girl]. / Sindrome HaNDL en una niña de 12 años.

INTRODUCTION: HaNDL (headache and neurological deficits with cerebrospinal fluid lymphocytosis) syndrome is a self-limiting benign condition which, as its name suggests, causes episodes of transient neurological deficits of a motor, sensory, aphasic and, less frequently, visual nature lasting several hours, accompanied or followed by moderate-to-severe headache and lymphocytosis of the cerebrospinal fluid. Its incidence is low in adulthood, and it is extremely uncommon in the paediatric age. Recurrence of episodes usually occurs in the first three months. It has an excellent prognosis. CASE REPORT: A 12-year-old female with intense frontal headache that suddenly begins on the tenth day, with clinical signs and symptoms of dysarthria and right hemiparesis with subsequent aphasia and generalised hypotonia. After ruling out other conditions by means of complementary examinations and the clinical course, the patient was finally diagnosed with HaNDL syndrome, since it fulfilled the clinical criteria of the International Headache Society (IHS). CONCLUSIONS: The patient met the criteria established by the IHS for the diagnosis of HaNDL syndrome. The main historical, epidemiological and clinical data are analysed and the differential diagnosis of HaNDL syndrome in the paediatric age is described.

TITLE: Sindrome HaNDL en una niña de 12 años.Introduccion. El sindrome HaNDL (headache and neurologic deficits with cerebrospinal fluid lymphocytosis) es una entidad autolimitada y benigna que cursa, como su nombre indica, con aparicion de episodios de deficits neurologicos transitorios de naturaleza motora, sensitiva o afasica, y menos frecuentemente visual, de varias horas de duracion, acompañados o seguidos de cefalea moderada-grave y linfocitosis del liquido cefalorraquideo. Su incidencia es baja en la edad adulta, y casi excepcional en la edad pediatrica. La recurrencia de los episodios suele producirse en los primeros tres meses. El pronostico es excelente. Caso clinico. Mujer de 12 años con cefalea frontal intensa que inicia en el decimo dia, de forma brusca, clinica de disartria y hemiparesia derecha con posterior afasia e hipotonia generalizada. Tras descartarse mediante exploraciones complementarias y evolucion clinica otras entidades, fue finalmente diagnosticada de sindrome HaNDL, ya que cumplia los criterios clinicos de la Sociedad Internacional de Cefaleas (IHS). Conclusiones. La paciente reunio los criterios de la IHS para el diagnostico de sindrome HaNDL. Se analizan los principales datos historicos, epidemiologicos y clinicos, y se expone el diagnostico diferencial del sindrome HaNDL en la edad pediatrica.

Borrelia lusitaniae Infection Mimicking Headache, Neurologic Deficits, and Cerebrospinal Fluid Lymphocytosis.

Headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare headache syndrome included in the Classification of Headache of the International Headache Society as a "headache attributed to non-infectious inflammatory intracranial disease." We report one 15-year-old patient with clinical history and cerebrospinal fluid findings compatible with the diagnosis of HaNDL in whom Borrelia lusitaniae was identified in cerebrospinal fluid by polymerase chain reaction.

Rheumatoid arthritis presenting as rheumatoid meningitis.

Rheumatoid meningitis (RM) is a rare extra-articular manifestation of rheumatoid arthritis (RA). A 59-year-old man presented with a 10-day history of right-sided frontal headache and a 7-day history of subacute left-sided weakness. He had no history of RA. He was febrile (38.2°C). Left ankle dorsiflexion and plantarflexion were graded at 4+/5. He developed focal onset motor seizures. He was intermittently febrile with minimal improvement despite intravenous antivirals and antimicrobials. Serology revealed elevated rheumatoid factor 88.2 IU/mL and anti-cyclic citrullinated peptide (anti-CCP) IgG >340 AU/mL. Initial cerebrospinal fluid (CSF) was predominantly lymphocytic 96%, with elevated protein 672 mg/L and normal glucose 3.4 mmol/L. Interval CSF revealed newly low glucose 2.6 mmol/L. Extensive CSF microbiology tests were negative. CSF cytology confirmed reactive lymphocytes. MRI brain revealed right frontoparietal leptomeningeal enhancement. Brain and leptomeningeal biopsy demonstrated florid leptomeningeal mixed inflammatory infiltrate without granulomas. The combination of elevated anti-CCP IgG, erosive arthropathy, CSF lymphocytosis, asymmetrical leptomeningeal enhancement and biopsy findings confirmed RM.

Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) in a patient with confusional symptoms, diffuse EEG abnormalities, and bilateral vasospasm in transcranial Doppler ultrasound: A case report and literature review. / Síndrome de cefalea transitoria con déficits neurológicos asociados y pleocitosis en líquido cefalorraquídeo (HaNDL) con cuadro confusional, EEG compatible con afectación difusa y datos de vasoespasmo bilateral en estudio Doppler transcraneal: presentación de un caso y revisión de la literatura.

INTRODUCTION: HaNDL syndrome (transient headache and neurological deficits with cerebrospinal fluid lymphocytosis) is characterised by one or more episodes of headache and transient neurological deficits associated with cerebrospinal fluid lymphocytosis. To date, few cases of HaNDL manifesting with confusional symptoms have been described. Likewise, very few patients with HaNDL and confusional symptoms have been evaluated with transcranial Doppler ultrasound (TCD). TCD data from patients with focal involvement reveal changes consistent with vasomotor alterations. DEVELOPMENT: We present the case of a 42-year-old man who experienced headache and confusional symptoms and displayed pleocytosis, diffuse slow activity on EEG, increased blood flow velocity in both middle cerebral arteries on TCD, and single-photon emission computed tomography (SPECT) findings suggestive of diffuse involvement, especially in the left hemisphere. CONCLUSIONS: To our knowledge, this is the first description of a patient with HaNDL, confusional symptoms, diffuse slow activity on EEG, and increased blood flow velocity in TCD. Our findings suggest a relationship between cerebral vasomotor changes and the pathophysiology of HaNDL. TCD may be a useful tool for early diagnosis of HaNDL.

HaNDL Syndrome: Case Report and Literature Review.

Headache and Neurologic Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) syndrome is a rare stroke mimicker characterized by moderate to severe headache temporally associated with transient neurologic deficits, typically hemiparesis, hemisensory disturbance, and/or aphasia. Cerebrospinal fluid studies reveal a lymphocytosis and elevated protein. Episodes recur over a period no longer than 3 months. Here we describe the case of a 16-year-old boy who presented with 3 episodes of self-resolving neurologic deficits, papilledema on fundoscopic examination, and leptomeningeal enhancement on magnetic resonance imaging (MRI). We additionally review the 30 previously reported pediatric cases of HaNDL syndrome, with a focus on possible etiologic and pathophysiologic mechanisms of disease. The reported case and literature review highlight the benign episodic nature of this likely underrecognized syndrome as well as the higher than expected frequency of abnormal neuroimaging findings.