Collaboration between a human group and artificial intelligence can improve prediction of multiple sclerosis course. A proof-of-principle study

Background: Multiple sclerosis has an extremely variable natural course. In most patients, disease starts with a relapsing-remitting (RR) phase, which proceeds to a secondary progressive (SP) form. The duration of the RR phase is hard to predict, and to date predictions on the rate of disease progression remain suboptimal. This limits the opportunity to tailor therapy on an individual patient's prognosis, in spite of the choice of several therapeutic options. Approaches to improve clinical decisions, such as collective intelligence of human groups and machine learning algorithms are widely investigated. Methods: Medical students and a machine learning algorithm predicted the course of disease on the basis of randomly chosen clinical records of patients that attended at the Multiple Sclerosis service of Sant'Andrea hospital in Rome. Results: A significant improvement of predictive ability was obtained when predictions were combined with a weight that depends on the consistence of human (or algorithm) forecasts on a given clinical record. Conclusions: In this work we present proof-of-principle that human-machine hybrid predictions yield better prognoses than machine learning algorithms or groups of humans alone. To strengthen this preliminary result, we propose a crowdsourcing initiative to collect prognoses by physicians on an expanded set of patients

Coincident onset of multiple sclerosis and herpes simplex virus 1 encephalitis. a case report

Background: Along with vitamin D, smoking, body mass index and others, Epstein Barr virus, other herpesviruses and human endogenous retroviruses represent plausible environmental risk factors for multiple sclerosis. However, it is difficult to obtain direct proof of their involvement in the etiology of this condition. Case presentation: In order to contribute further evidence of the importance of these viruses, and speculate about disease-relevant interactions between these agents and a predisposed genetic background of the host, we describe the temporal association between multiple sclerosis onset and Herpes simplex 1-encephalitis in a female patient. Conclusions: This case illustrates a possible relationship between HSV-1 encephalitis and multiple sclerosis. Bearing in mind that association does not imply causation, some speculations about the etiology and pathophysiology of the two diseases can be made. The hypothesis of a genetic background predisposing to HSV-1 encephalitis and to immune-mediated demyelination is supported by the coincidence of the two conditions in this patient, along with data from animal models and genetic studies

Leptomeningitis in a person with radiologically isolated syndrome and latent tuberculosis. A case report with implications for clinical research

A 39-year-old man, followed with serial MRI of CNS for a radiologically isolate syndrome (RIS, a recently described condition considered a subclinical form of MS), was hospitalized for the occurrence of a leptomeningitis. Routine blood tests and contrast enhanced total body CT scan were unremarkable. Cerebrospinal fluid (CSF) examination showed increase of cells (22 mononuclear cells/mm3), albumin (294 mg/L), immunoglobilins G (161 mg/L) and Link Index (1.9), with 17 oligoclonal bands. Microbiological examinations of CSF (including those for Koch’s Bacillus) were negative. The Mantoux reaction and the QuantiFERON test were positive, featuring a latent tuberculosis (TB). The patient started prophylaxis with rifampicin and isoniazid for four months, until a new MRI showed the disappearance of the leptomeningeal enhancement, and the stability of white matter brain and spinal cord lesions. Two other MRI scans showed a new brain Gd-enhancing lesion nine month after anti-tubercular therapy and, after additional six months, new cerebral and spinal cord areas. This case provides the following suggestions about the effects of TB infection and related therapies on the underlying autoimmune status: the infection, while actively present, did not exacerbate the RIS condition; the worsening nine months after the prophylaxis discontinuation might have been the ‘natural’ evolution of RIS condition. Alternative speculative hypotheses include a remote effect of the infection, of isoniazid (that was reported in some cases to trigger MS), or the result of the clearance of the infection itself. Irrespective of the existence of any interaction between RIS and TB infection, It seems important to collect cases with MS-related diseases and concomitant infections, that may provide clues about disease pathogenesis and treatment

Novel homozygous GBA2 mutation in a patient with complicated spastic paraplegia

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurological disorders characterized primarily by a pyramidal syndrome with lower limb spasticity, which can manifest as pure HSP or associated with a number of neurological or non-neurological signs (i.e., complicated HSPs). The clinical variability of HSPs is associated with a wide genetic heterogeneity, with more than eighty causative genes known. Recently, next generation sequencing (NGS) has allowed increasing genetic definition in such a heterogeneous group of disorders. We report on a 56- year-old man affected by sporadic complicated HSP consisting of a pyramidal syndrome, cerebellar ataxia, congenital cataract, pes cavus, axonal sensory-motor peripheral neuropathy and cognitive decline. Brain MRI showed cerebellar atrophy and thin corpus callosum. By NGS we found a novel homozygous biallelic c.452-1G > C mutation in the b-glucosidase 2 gene (GBA2), known to be causative for autosomal recessive hereditary spastic paraplegia type 46 (SPG46). The rarity of this inherited form besides reporting on a novel mutation, expands the genetic and clinical spectrum of SPG46 related HSP

Genome-Wide Multiple Sclerosis Association Data and Coagulation

The emerging concept of a crosstalk between hemostasis, inflammation, and immune system prompt recent works on coagulation cascade in multiple sclerosis (MS). Studies on MS pathology identified several coagulation factors since the beginning of the disease pathophysiology: fibrin deposition with breakdown of blood brain barrier, and coagulation factors within active plaques may exert pathogenic role, especially through the innate immune system. Studies on circulating coagulation factors showed complex imbalance involving several components of hemostasis cascade (thrombin, factor X, factor XII). To analyze the role of the coagulation process in connection with other pathogenic pathways, we implemented a systematic matching of genome-wide association studies (GWAS) data with an informative and unbiased network of coagulation pathways. Using MetaCore (version 6.35 build 69300, 2018) we analyzed the connectivity (i.e., direct and indirect interactions among two networks) between the network of the coagulation process and the network resulting from feeding into MetaCore the MS GWAS data. The two networks presented a remarkable over-connectivity: 958 connections vs. 561 expected by chance; z-score = 17.39; p-value < 0.00001. Moreover, genes coding for cluster of differentiation 40 (CD40) and plasminogen activator, urokinase (PLAU) shared both networks, pointed to an integral interplay between coagulation cascade and main pathogenic immune effectors. In fact, CD40 pathways is especially operative in B cells, that are currently a major therapeutic target in MS field. The potential interaction of PLAU with a signal of paramount importance for B cell pathogenicity, such as CD40, suggest new lines of research and pave the way to implement new therapeutic targets

Progression of motor subtypes in Huntington’s disease. a 6-year follow-up study

The objective of this study is to investigate the progression of predominantly choreatic and hypokinetic-rigid signs in Huntington's disease (HD) and their relationship with cognitive and general functioning over time. The motor signs in HD can be divided into predominantly choreatic and hypokinetic-rigid subtypes. It has been reported in cross-sectional studies that predominantly choreatic HD patients perform better on functional and cognitive assessments compared to predominantly hypokinetic-rigid HD patients. The course of these motor subtypes and their clinical profiles has not been investigated longitudinally. A total of 4135 subjects who participated in the European HD Network REGISTRY study were included and classified at baseline as either predominantly choreatic (n = 891), hypokinetic-rigid (n = 916), or mixed-motor (n = 2328), based on a previously used method. The maximum follow-up period was 6 years. The mixed-motor group was not included in the analyses. Linear mixed models were constructed to investigate changes in motor subtypes over time and their relationship with cognitive and functional decline. Over the 6-year follow-up period, the predominantly choreatic group showed a significant decrease in chorea, while hypokinetic-rigid symptoms slightly increased in the hypokinetic-rigid group. On the Total Functional Capacity, Stroop test, and Verbal fluency task the rate of change over time was significantly faster in the predominantly choreatic group, while on all other clinical assessments the decline was comparable for both groups. Our results suggest that choreatic symptoms decrease over time, whereas hypokinetic-rigid symptoms slightly increase in a large cohort of HD patients. Moreover, different motor subtypes can be related to different clinical profiles

When a pregnancy required a neurological consultation: a case report

Posterior reversible encephalopathy syndrome (PRES) is a transient clinical and neuroradiological syndrome characterized by clinical signs and symptoms including hypertension, seizures, altered mental status, headache, and vision changes and characteristic features on head computed tomography (CT) or magnetic resonance imaging (MRI) scan. PRES is most commonly reported in the literature in association with obstetric patients suffering from pre-eclampsia or eclampsia. In the acute setting, it is important to recognize the characteristics of PRES and immediately treat patients' emerging conditions that are hypertension and seizures. The following case report describes a pregnant patient who presented clinical characteristics of eclampsia with recurrent episodes of seizure and hypertension complicated by PRES. This case highlights the importance of early recognition and treatment of this condition that is usually transient and completely reversible, but can lead to ischemic injury and irreversible brain damage. Clin Ter 2012; 163(6):487-49

Vaccines in multiple sclerosis. The experience of BCG vaccination

Despite earlier reports showing an onset of multiple sclerosis (MS) or the occurrence of relapses after vaccination, more recent large epidemiological studies did not find this association and confirmed the safety of common compulsory vaccinations in MS. Moreover, experimental and epidemiological evidence suggests benefit of exposure to microbial products (in the absence of infection, as is the case of vaccination) in MS. Along this line, Bacillus Calmette-Guerin (BCG) vaccine was tried in early MS and resulted safe and effective in reducing disease activity on magnetic resonance imaging, as well as the risk of developing persistent T1-hypointense lesions ("black holes" - expression of tissue damage). Another trial in people with clinically isolated syndromes demonstrated a benefit of BCG with respect to the conversion to clinically definite MS over 5 years. These results suggest the use of BCG immediately after disease onset. Even the possible extension to people at risk of MS might be envisioned, given that the approach is safe, inexpensive and convenient