Consensus Paper: Latent Autoimmune Cerebellar Ataxia (LACA).

Immune-mediated cerebellar ataxias (IMCAs) have diverse etiologies. Patients with IMCAs develop cerebellar symptoms, characterized mainly by gait ataxia, showing an acute or subacute clinical course. We present a novel concept of latent autoimmune cerebellar ataxia (LACA), analogous to latent autoimmune diabetes in adults (LADA). LADA is a slowly progressive form of autoimmune diabetes where patients are often initially diagnosed with type 2 diabetes. The sole biomarker (serum anti-GAD antibody) is not always present or can fluctuate. However, the disease progresses to pancreatic beta-cell failure and insulin dependency within about 5 years. Due to the unclear autoimmune profile, clinicians often struggle to reach an early diagnosis during the period when insulin production is not severely compromised. LACA is also characterized by a slowly progressive course, lack of obvious autoimmune background, and difficulties in reaching a diagnosis in the absence of clear markers for IMCAs. The authors discuss two aspects of LACA: (1) the not manifestly evident autoimmunity and (2) the prodromal stage of IMCA's characterized by a period of partial neuronal dysfunction where non-specific symptoms may occur. In order to achieve an early intervention and prevent cell death in the cerebellum, identification of the time-window before irreversible neuronal loss is critical. LACA occurs during this time-window when possible preservation of neural plasticity exists. Efforts should be devoted to the early identification of biological, neurophysiological, neuropsychological, morphological (brain morphometry), and multimodal biomarkers allowing early diagnosis and therapeutic intervention and to avoid irreversible neuronal loss.

Contrasting features between Tourette syndrome and secondary tic disorders.

Tics are rapid, recurrent, non-rhythmic movements or emitted sounds. Tics are the hallmark of Tourette syndrome (TS); however, a number of other disorders may be associated with tics, so-called secondary tic disorders (STD). We assessed clinical history and performed blinded evaluations of video-recordings from patients with TS and STD in order to identify features that may differentiate tics associated with TS vs STD. There were 156 patients with TS and 38 with STD, 21 of whom had functional (psychogenic) tics. Patients with TS were more frequently male and had a younger age at onset. Tics in TS tend to involve muscles in the cranial-cervical area more often and have greater severity and complexity than those in patients with STD. Similar findings were observed when contrasting patients with TS with patients with functional tics only. Simple phonic tics showed the greatest diagnostic accuracy for TS, compared with STD, but marked overlap in the types of tics and comorbidities was observed between patients with TS and STD. Patients with TS were more likely males, had a younger age at onset, phonic tics and motor tics affecting predominantly the head and neck area, and had a greater complexity and severity of tics than those with STD. When these features are absent a consideration should be given to the possibility of a tic disorder other than TS.

Sex differences in patients with Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and phonic tics. It is at least three times more common in males compared with females; however, the clinical phenomenology between sexes has not been fully examined. We aimed to contrast the clinical features between males and females with TS and chronic tic disorder. METHODS: We studied 201 consecutive patients fulfilling the diagnostic criteria for TS, persistent (or chronic) motor and vocal tic disorder and provisional tic disorder that were considered within the TS spectrum disorder. We performed blinded evaluations of video-recordings and retrospectively reviewed the clinical charts of all patients. RESULTS: Age ranges between 4 and 65 years. Males represented 77.6% of patients in the cohort. Overall, no differences were observed in the frequency, distribution and complexity of tics between sexes, except for a higher frequency of attention-deficit/hyperactivity disorder (ADHD) (P = .003) among males. Patients younger than 18-years old, in addition to a higher frequency of ADHD (P = .026), males had a statistically higher frequency of complex motor tics (P = .049) and earlier age at onset (P = .072) than females in the multivariate regression analysis. However, these differences were lost in patients older than 18 years, due to increased complexity of tics in females with aging. CONCLUSIONS: A sexual dimorphism was observed between patients with TS mainly before age of 18 years, suggesting an earlier onset of some types of tics and ADHD in males compared to females.

Beyond tics: movement disorders in patients with Tourette syndrome.

BACKGROUND: Tics are the hallmark of Tourette syndrome (TS). However, TS patients may have a particular vulnerability to develop other movement disorders (MDs), such as dystonia, chorea, stereotypy, and other hyperkinetic disorders that may be wrongly attributed to tics. MATERIALS AND METHODS: We studied a cohort of 201 patients with motor and phonic tics associated with TS to determine if they have additional, co-existent, MDs. RESULTS: There were 67 (33.3%) patients with comorbid non-tic MDs. Phenomenology-wise, piano-playing movements resembling chorea or myoclonus, were the most common non-tic movement, observed in 11% of cases, followed by stereotypies (8.0%), tremor, dystonia and parkinsonism, 5.0% each. Drug-induced was the most common etiology (6.0%), followed by functional movement disorders (5.0%) and tardive phenomena (5.0%). No clear etiology was identified in most patients. Piano-playing movements, were associated with a younger age at onset (P = 0.004) and younger age at presentation (P < 0.001). Patients with drug-induced movements and tardive phenomena had a lower frequency of craniofacial tics. FMDs, and idiopathic MDS showed no specific associations with TS. Tic severity was not a predictor of any co-existent MD. CONCLUSION: About a third of patients with TS present with comorbid MDs which should be differentiated and distinguished from tics as their etiopathogenesis and treatment may be different.

Chorea in children: etiology, diagnostic approach and management.

Chorea is defined by the presence of abnormal, involuntary, continuous, random movements that results from a number of autoimmune, hereditary, vascular, metabolic, drug-induced and functional (psychogenic) causes. Chorea may present at all stages of life, from newborns to elderly individuals. While Huntington disease is the main suspicion in adults presenting with chorea, once a drug-induced or parkinsonian dyskinesia have been ruled out; Huntington disease exceptionally presents with chorea in children. Sydenham chorea is considered the most common cause of acute childhood-onset chorea, but its prevalence has decreased in Western countries. However, in younger children other etiologies such as dyskinetic cerebral palsy, anti-NMDAR receptor encephalitis, other autoimmune conditions, or mutations in NKX2-1, ADCY-5, FOXG1, GNAO1, GPR88, SLC2A1, SQSTM1, ATP8A2, or SYT-1 should be considered. In this manuscript, we review the main causes, diagnosis and management of chorea in children.

Functional gait disorders, clinical phenomenology, and classification.

BACKGROUND: Functional gait disorders (FGDs) are relatively common in patients presenting for evaluation of a functional movement disorder (FMD). The diagnosis and classification of FGDs is complex because patients may have a primary FGD or a FMD interfering with gait. METHODS: We performed a detailed evaluation of clinical information and video recordings of gait in patients diagnosed with FMDs. RESULTS: We studied a total of 153 patients with FMDs, 68% females, with a mean age at onset of 36.4 years. A primary FGD was observed in 39.2% of patients; among these patients, 13 (8.5%) had an isolated FGD (a gait disorder without other FMDs). FMDs presented in 34% of patients with otherwise normal gait. Tremor was the most common FMD appearing during gait, but dystonia was the most common FMD interfering with gait. Patients with FGD had a higher frequency of slow-hesitant gait, astasia-abasia, bouncing, wide-based gait and scissoring compared with patients with FMDs occurring during gait. Bouncing gait with knee buckling was more frequently observed in patients with isolated FGD (P = 0.017). Patients with FGDs had a trend for higher frequency of wheelchair dependency (P = 0.073) than those with FMDs interfering with gait. CONCLUSIONS: Abnormal gait may be observed as a primary FGD or in patients with other FMDs appearing during gait; both conditions are common and may cause disability.

Pathogenesis and pathophysiology of functional (psychogenic) movement disorders.

Functional movement disorders (FMDs), known over time as "hysteria", "dissociative", "conversion", "somatoform", "non-organic" and "psychogenic" disorders, are characterized by having a voluntary quality, being modifiable by attention and distraction but perceived by the patient as involuntary. Although a high prevalence of depression and anxiety is observed in these patients, a definitive role of psychiatric disorders in FMDs has not been proven, and many patients do not endorse such manifestations. Stressful events, social influences and minor trauma may precede the onset of FMDs, but their pathogenic mechanisms are unclear. Patients with FMDs have several abnormalities in their neurobiology including strengthened connectivity between the limbic and motor networks. Additionally, there is altered top-down regulation of motor activities and increased activation of areas implicated in self-awareness, self-monitoring, and active motor inhibition such as the cingulate and insular cortex. Decreased activation of the supplementary motor area (SMA) and pre-SMA, implicated in motor control and preparation, is another finding. The sense of agency defined as the feeling of controlling external events through one's own action also seems to be impaired in individuals with FMDs. Correlating with this is a loss of intentional binding, a subjective time compression between intentional action and its sensory consequences. Organic and functional dystonia may be difficult to differentiate since they share diverse neurophysiological features including decreased cortical inhibition, and similar local field potentials in the globus pallidus and thalamus; although increased cortical plasticity is observed only in patients with organic dystonia. Advances in the pathogenesis and pathophysiology of FMDs may be helpful to understand the nature of these disorders and plan further treatment strategies.

The neurological syndromes associated with glutamic acid decarboxylase antibodies.

A number of neurological syndromes have been described in patients with positive serum antibodies (Abs) against the enzyme glutamic acid decarboxylase (GAD), the rate limiting step in the synthesis of GABA (γ-aminobutyric acid). These disorders include: classical stiff-person syndrome and variants, cerebellar ataxia, limbic and extra-limbic encephalitis, nystagmus/oculomotor dysfunction, drug-resistant epilepsy, paraneoplastic stiff-person syndrome and progressive encephalopathy with rigidity and myoclonus (PERM), the latter two are mainly related to amphiphysin and the glycine receptor Abs respectively; but patients may also have positive GAD-Abs. Although observations are consistent with an autoimmune response in these patients and there is evidence of GABAergic dysfunction in some cases; the pathogenic role of GAD-Abs in the nervous system has not been clarified and it is a matter of debate. The diagnosis of these syndromes is based on clinical grounds plus the presence of GAD-Abs in serum and CSF with demonstration of intrathecal secretion. Although some presentations may be negative for GAD-Abs, such as stiff-person syndrome; positive GAD-Abs are required for the diagnosis in patients with cerebellar ataxia, encephalitis, and epilepsy. Immunotherapy is required for most patients. Intravenous immunoglobulins, oral or IV steroids and plasma exchange are considered the first line options, aimed to induce remission, but chronic immunosuppression is usually required. Symptomatic therapy should also be provided, aimed to control muscle spasms, seizures, delirium, etc. Prognosis varies among patients; but it is considered intermediate between that of patients with neurological syndromes associated with neural Abs against membrane antigens and those with onconeural Abs.

Clinical correlations of striatal hand deformities in Parkinson's disease.

BACKGROUND: Hand deformities have been recognized since the 19th century as part of the postural abnormalities observed in Parkinson's disease (PD). However, their pathogenesis and clinical correlations are poorly understood. METHODS: We evaluated 104 hands of 52 consecutive patients with PD by high-resolution photographs taken from the radial aspect of each hand; the degree of flexion of the 2nd metacarpophalangeal (MCP) joint was measured by software. The presence of classical striatal hand deformity (CSHD) was also evaluated, defined as MCP flexion, proximal interphalangeal joint extension, and distal interphalangeal joint flexion. RESULTS: Patients with PD had a mean age of 63.3 ± 12.7 years, and 29 (56%) were male. The degree of MCP joint flexion in both hands showed moderate correlation with the MDS-UPDRS-III motor score (r = 0.518, P < 0.001), mainly related to ipsilateral rigidity and ipsilateral bradykinesia scores, and fair correlation with the Hoehn-Yahr stage. A CSHD only correlated with a younger age at onset of PD (P = 0.049). These hand deformities were not markers of dyskinesia, levodopa equivalent dose, or cognitive dysfunction. CONCLUSIONS: Metacarpophalangeal joint flexion is the most common hand deformity in PD and correlates with rigidity and bradykinesia. A CSHD was only related to a younger age at onset.

The frequency and diagnostic accuracy of hand deformities in Parkinson's disease.

Hand deformities are well-known abnormalities observed in patients with Parkinson's disease (PD). We determined the frequency and diagnostic accuracy of hand deformities in PD. We studied 44 consecutive patients with PD, 44 age- and gender-matched normal controls and 22 patients with essential tremor (ET). By means of photographs taken in both hands of all participants, the degree of metacarpophalangeal (MCP) joint flexion was quantified by software and by blinded evaluations using a semiquantitative scale from the radial aspect, we grouped hands into four grades. The presence of classical striatal hand deformity (CSHD), defined as MCP joint flexion, proximal interphalangeal joint extension and distal interphalangeal joint flexion was also evaluated. Patients with PD had a higher frequency of MCP joint flexion and CSHD compared to normal controls and patients with ET. Mean MCP joint flexion was higher in both hands in patients with PD: 20.8° vs. normal controls (3.3°-3.9°) and patients with ET (2.8°-6.3°), P = 0.001. Concordance between evaluators for MCP joint flexion was fair: κ = 0.34 (P < 0.001), but poor for CSHD: κ = 0.142-0.235 (P < 0.05). A right hand MCP joint flexion of 12.5° and left hand of 10.5°, showed similar sensitivity (0.70) and specificity (between 0.75 and 0.80) than any degree of MCP joint flexion for the diagnosis of PD. CSHD had a sensitivity (0.60-0.80) and specificity (0.78-0.98) for the diagnosis of PD. Hand deformities are commonly observed in patients with PD, they may aid in the diagnosis of PD when compared to normal controls and patients with ET.

Cerebellar disease associated with anti-glutamic acid decarboxylase antibodies: review.

Several neurological syndromes have been recognized associated to GAD antibodies. Among those disorders, cerebellar ataxia (CA) is one of the most common, along with stiff-person syndrome. Patients with GAD associated CA present with a progressive pancerebellar syndrome, with a subacute or chronic evolution, along with other neurological manifestations such as stiffness, oculomotor dysfunction, epilepsy, and cognitive dysfunction. These symptoms may be preceded by the so-called "brainstem attacks", where manifestations consistent with transient dysfunction of the brainstem may be observed. These patients frequently have extra-neurologic autoimmune manifestations such as diabetes mellitus type 1, polyendocrine autoimmune syndrome, pernicious anemia, vitiligo, etc. A proportion of patients may present with an underlying neoplasia, but the course is less aggressive than in those patients with classical paraneoplastic CA with onconeural antibodies. The diagnosis is based on the present of high serum and CSF titers of GAD antibodies, with intrathecal production of such antibodies. Treatment is aimed to decrease the immunological response with intravenous immunoglobulin, steroids, rituximab and oral immunosuppressive drugs. A subacute presentation and rapid initiation of immunotherapy seem to be the predictors of a favorable clinical response.

Psychogenic Ophthalmologic Movement Disorders.

In this study, the authors retrospectively identified 11 patients with psychogenic ophthalmologic movement disorders (POMDs) (6%) among 182 patients with psychogenic movement disorders (PMDs), using medical charts and video reviews. The phenomenology included oculogyric crises (N=7), opsoclonus (N=5), and ocular flutter (N=1). No statistically significant differences were observed in gender and PMD distribution between patients with and without POMDs, although a trend for younger age at onset was observed in patients with POMDs. Seven patients showed improvement with psychotherapy, whereas two patients with persistent ocular supraversion and blepharospasm failed to improve. Based on our own series and review of literature, we conclude that POMDs contribute to the overall morbidity in patients affected with PMDs.

Stiff-person syndrome: insights into a complex autoimmune disorder.

Stiff-person syndrome (SPS) is characterised by progressive rigidity and muscle spasms affecting the axial and limb muscles. Since its initial description in 1956, marked progress has been made in the clinical characterisation, understanding of pathogenesis and therapy of this disorder. SPS can be classified according to the clinical presentation into classic SPS and SPS variants: focal or segmental-SPS, jerking-SPS and progressive encephalomyelitis with rigidity and myoclonus. Most patients with SPS have antibodies directed against the glutamic acid decarboxylase, the rate-limiting enzyme for the production of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Antibodies directed against GABA(A) receptor-associated protein, and the glycine-α1 receptor can also be observed. Paraneoplastic SPS is commonly associated with antiamphiphysin antibodies and breast cancer. Treatment of SPS with drugs that increase the GABAergic tone combined with immunotherapy can improve the neurological manifestations of these patients. The prognosis, however, is unpredictable and spontaneous remissions are unlikely.

Myorhythmia: phenomenology, etiology, and treatment.

Myorhythmia is defined as repetitive, rhythmic, slow (1-4 Hz) movement affecting chiefly cranial and limb muscles. When occurring in the limbs it may be oscillatory and jerky, whereas oculo-masticatory myorhythmia, typically associated with Whipple's disease, is a slow, repetitive, often asymmetrical, facial and ocular movement. Thus, myorhythmia overlaps phenomenologically with tremor and segmental myoclonus. Although often present at rest, it must be differentiated from parkinsonian or dystonic tremor. Recognition of this movement disorder is important because it is usually associated with lesions involving the brainstem, thalamus, or other diencephalic structures with potentially treatable etiologies. In addition to Whipple's disease, myorhythmia has been described in patients with cerebrovascular disease, listeria encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, steroid-responsive encephalopathy associated with autoimmune thyroiditis, multiple sclerosis, and other disorders. In addition to our own experience, we have systematically reviewed the medical literature, focusing on the phenomenology, pathophysiology, and etiology of this poorly recognized movement disorder. In this review, we aim to highlight the clinical features that differentiate myorhythmia from other movement disorders. Treatment should be directed against the underlying etiology.

The clinical features of psychogenic movement disorders resembling tics.

BACKGROUND: Psychogenic movement disorders (PMDs) may be difficult to differentiate from organic abnormal movements. METHODS: We aimed to characterise the prevalence and clinical features of PMDs resembling tics during the last 3.5 years in our centre. RESULTS: We studied 9 patients (five females) with psychogenic tics representing 4.9% of all 184 patients first evaluated for a PMD during the study period. The mean age at onset was 34.1 years. Lack of premonitory sensations, absence childhood and family history of tics, inability to suppress the movements and coexistence with other PMDs and pseudoseizures were common in our patients. Compared with 273 patients with Tourette syndrome, those with PMDs resembling tics were older: 36.3 versus 18.7 years (p=0.014) at presentation and more frequently female (p=0.030). CONCLUSIONS: Movements resembling tics are observed in a small proportion of patients with PMDs. Clinical features can help to differentiate them from organic tics.

The safety and efficacy of thalamic deep brain stimulation in essential tremor: 10 years and beyond.

BACKGROUND: Deep brain stimulation (DBS) has proven to be a safe and effective therapy for refractory essential tremor, but information regarding long-term outcomes is lacking. OBJECTIVES: We aimed to assess the long-term safety and efficacy of DBS in patients with essential tremor. METHODS: Patients treated with DBS for essential tremor for at least 8 years were evaluated in the 'on' and 'off' state using the Fahn-Tolosa-Marin tremor rating scale, and their medical records were reviewed to assess complications related to this therapy. RESULTS: We studied 13 patients (7 men): median age at evaluation 79 years (range 47-88), median age at electrode implantation 68 years (range 37-78) and mean time since electrode implantation 132.54±15.3 months (range 114-164). The difference between the 'off' and 'on' state on the motor items of the tremor rating scale was 41.9% (58.62 vs. 34.08, p<0.001) in the non-blinded and 37.2% (56.07 vs. 35.23, p<0.001) in the blinded rating. DBS provided a functional improvement of 31.7% in the 'on' state (15.07 vs. 22.07, p<0.001). A total non-blinded improvement in the tremor rating scale of 39% was observed in the 'on' state (49.15 vs. 80.69, p<0.001). Dysarthria and disequilibrium were common in patients with bilateral stimulation. A DBS-related surgery (electrode revision or internal pulse generator exchange) was necessary on average every 47.9 months to continue with the DBS therapy. CONCLUSIONS: Thalamic DBS is a safe and effective therapy in patients with essential tremor followed for up to 13 years.

Clinical deterioration following middle cerebral artery hemodynamic changes after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND: Little information exists regarding what occurs in the affected artery in the days after acute ischemic stroke and its impact in the outcome. We sought to determine the hemodynamic evolution and correlated this evoution with clinical outcome in stroke patients treated with intravenous thrombolysis. METHODS: Using serial transcranial Doppler ultrasound (TCD) on days 1 (TCD1), 3 to 6 (TCD2), and 7 to 10 (TCD3) after stroke, we determined the hemodynamics in the affected artery by means of the thrombolysis in brain ischemia (TIBI) score and compared this with clinical outcome (National Institutes of Health Stroke Scale [NIHSS] score) and functional outcome (modified Rankin Scale score) at discharge and at 3 months. RESULTS: Thirty-four patients were studied. There were 24 men with a mean (± SD) age of 72.9 ± 16.2 years. The mean time from stroke onset to the administration of intravenous tissue plasminogen activator was 181 ± 54.4 minutes, and the mean NIHSS score at admission was 16.9 ± 9. Hemodynamic changes were observed in 23 (68%) patients, including improvement in 17 (50%) patients and worsening in 6 (18%) patients within the first 10 days poststroke. Clinical deterioration (NIHSS ≥4 points) was timely associated with hemodynamic deterioration in 3 cases. Patients achieving full recanalization at TCD3 had better mRS scores at 3 months (4 v 3; P = .02). CONCLUSIONS: Hemodynamic changes in the affected artery occurred in about two-thirds of patients within the first 10 days after receiving intravenous thrombolysis; 18% had hemodynamic deterioration, which was associated with clinical worsening in half of these cases.

Tics emergencies and malignant tourette syndrome: Assessment and management.

Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the presence of tics, frequently accompanied by a variety of neuropsychiatric comorbidities. A subset of patients with TS present with severe and disabling symptoms, requiring prompt therapeutic intervention. Some of these manifestations may result in medical emergencies when severe motor or phonic tics lead to damage of anatomical structures closely related to the tic. Examples include myelopathy or radiculopathy following severe neck ("whiplash") jerks or a variety of self-inflicted injuries. In addition to self-aggression or, less commonly, allo-aggression, some patients exhibit highly inappropriate behavior, suicidal tendencies, and rage attacks which increase the burden of the disease and are important components of "malignant TS". This subset of TS is frequently associated with comorbid obsessive-compulsive disorder. Therapeutic measures include intensive behavioral therapy, optimization of oral pharmacotherapy, botulinum toxin injections, and deep brain stimulation.

IgLON5 autoimmunity in a patient with Creutzfeldt-Jakob disease: case report and review of literature.

Objective: We present the case of a patient with clinical and imaging features of sporadic Creutzfeldt-Jakob disease (sCJD) and positive IgLON5 antibodies (Abs) in the serum and CSF. Case report: A 66-year-old Chinese man presented to the hospital with a stroke-like episode, followed by rapidly progressive cognitive decline, mutism, and parkinsonism. The MRI results showed a cortical ribboning sign in diffusion-weighted MRI, periodic triphasic waves with a slow background in EEG, and positive protein 14-3-3 in CSF. There were matching IgLON5 Abs in the serum and CSF. A literature review showed positive autoimmune encephalitis Abs or autoimmune inflammatory disease between 0.5 and 8.6% among patients with clinical suspicion of CJD, most commonly anti-voltage-gated potassium channel (VGKC) complex and anti-N-methyl-D-aspartate receptor (NMDAR) Abs; however, IgLON5 autoimmunity in CJD has been rarely reported. This is an intriguing association as both conditions have been associated with brain deposits of phosphorylated tau protein. Conclusion: IgLON5 Abs may be observed in patients with a diagnosis of CJD; it is unknown whether a synergistic effect of IgLON5 Abs with CJD exists, increasing neurodegenerative changes.

Metagenomic next-generation sequencing assistance in identifying Mycobacterium avium meningoencephalitis: A case report and literature review.

Nontuberculous mycobacteria associated intracranial infection is a rare disease that mainly occurs in HIV-infected patients. The disease has a poor prognosis. The authors report a case of non-tuberculous mycobacterial meningoencephalitis in a non-AIDS patient, but long history of poorly controlled type 2 diabetes mellitus. A 55-year-old, right-handed, male patient presented with an 8-day history of fever, episodes of severe headache with signs of meningeal irritation. MRI showed hyperintensities/contrast enhancement in the visual pathways, basal ganglia sellar region and leptomeninges. No etiological diagnosis was reached until metagenomic next-generation sequencing (mNGS) was used, showing the presence of Mycobacterium avium. The patient was cured with aggressive antimycobacterial therapy. The authors discuss the clinical manifestations and drug therapy of nontuberculous mycobacteria-related intracranial infections by reviewing relevant literature. As meningoencephalitis by Mycobacterium avium has a high mortality an early diagnosis and appropriate therapeutic interventions are warranted. For this reason, the use of mNGS can be helpful to avoid therapeutic delay.