Headaches and Vasculitis.

Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system leads to pervasive injury and disability making this a disorder of paramount importance to all clinicians. Headache may be an important clue to vasculitic involvement of central nervous system (CNS) vessels.

Systemic vasculitis and headache.

Purpose Of Review: Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system or so called neurovasculitides, lead to pervasive injury and disability making these disorder of paramount importance to clinicians.

Recent Findings: Headache is an important clue to vasculitic involvement of central nervous system (CNS) vessels.

Primary central nervous system vasculitis and headache: Ten themes.

Purpose Of Review: The primary central nervous system (CNS) vasculitides refers to clinicopathologic disorders that share the histopathology of inflammation of cerebral or spinal blood vessels. Unrecognized and therefore untreated, vasculitis of the CNS results in irreversible injury and disability making these disorders of paramount importance to clinicians.

Recent Findings: Headache is an important clue to vasculitic involvement of CNS vessels.

Mesenchymal Stromal Cells Facilitate Neutrophil-Trained Immunity by Reprogramming Hematopoietic Stem Cells.

Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune-suppressive therapies. Trained immunity is a promising strategy to reduce this burden of disease. We previously demonstrated that mesenchymal stromal cells (MSCs) preconditioned with a class A CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) agonist, can augment emergency granulopoiesis in a murine model of neutropenic sepsis.

Mild traumatic brain injury and sports-related concussion.

Mild traumatic brain injury (mTBI) and concussion are equivalent terms for the sequela of injury to the head that disrupts brain functioning. Various forces may be causative from seemingly innocuous bumps to the head resulting from sports-related injuries to more severe blows to the head. However, the postconcussive motor, cognitive, emotional, and psychosocial sequelae can be just as devastating and long lasting, leading to loss of independent function and safe performance of activities.

Childhood spinal muscular atrophy.

Spinal muscular atrophy (SMA) is caused by biallelic mutations in the SMN1 (survival motor neuron 1) gene on chromosome 5q13.2, which leads to a progressive degeneration of alpha motor neurons in the spinal cord and in motor nerve nuclei in the caudal brainstem. It is characterized by progressive proximally accentuated muscle weakness with loss of already acquired motor skills, areflexia and, depending on the phenotype, varying degrees of weakness of the respiratory and bulbar muscles.

Pediatric neuropsychiatric disorders with motor and nonmotor phenomena.

The concept of pediatric autoimmune neuropsychiatric disorders associated with group A beta-hemolytic streptococcus (PANDAS) has become seminal since first introduced more than two decades ago. At the time of this writing, most neurologists, pediatricians, psychiatrists, and general pediatricians will probably have heard of this association or treated an affected child with PANDAS. The concept of an acute-onset, and typically self-limited, postinfectious autoimmune neuropsychiatric disorder resembling PANDAS manifesting vocal and motor tics and obsessive-compulsive disorder has broadened to other putative microbes and related endogenous and exogenous disease triggers.

Motor sequela of adult and pediatric stroke: Imminent losses and ultimate gains.

Stroke is the leading cause of neurological disability in the United States and worldwide. Remarkable advances have been made over the past 20 years in acute vascular treatments to reduce infarct size and improve neurological outcome. Substantially less progress has been made in the understanding and clinical approaches to neurological recovery after stroke.

Spinal cord motor disorders.

Spinal cord diseases are frequently devastating due to the precipitous and often permanently debilitating nature of the deficits. Spastic or flaccid paraparesis accompanied by dermatomal and myotomal signatures complementary to the incurred deficits facilitates localization of the insult within the cord. However, laboratory studies often employing disease-specific serology, neuroradiology, neurophysiology, and cerebrospinal fluid analysis aid in the etiologic diagnosis.

Paraneoplastic motor disorders.

Paraneoplastic neurological disorders (PNDs) are heterogeneous clinicopathologic syndromes that occur throughout the neuraxis resulting from damage to organs or tissues remote from the site of a malignant neoplasm or its metastases. The discordance between severe neurological disability and even an indolent malignancy suggests an underlying neuroimmunologic host immune response that inflicts nervous tissue damage while inhibiting malignant tumor growth. Motor system involvement, like other symptoms and signs, is associated with focal or diffuse involvement of the brain, spinal cord, peripheral nerve, neuromuscular junction or muscle, alone or in combination due to an underlying neuroimmune and neuroinflammatory process targeting neural-specific antigens.

Amyotrophic lateral sclerosis.

The scientific landscape surrounding amyotrophic lateral sclerosis has shifted immensely with a number of well-defined ALS disease-causing genes, each with related phenotypical and cellular motor neuron processes that have come to light. Yet in spite of decades of research and clinical investigation, there is still no etiology for sporadic amyotrophic lateral sclerosis, and treatment options even for those with well-defined familial syndromes are still limited. This chapter provides a comprehensive review of the genetic basis of amyotrophic lateral sclerosis, highlighting factors that contribute to its heritability and phenotypic manifestations, and an overview of past, present, and upcoming therapeutic strategies.

Multiple sclerosis: Motor dysfunction.

Multiple sclerosis is a chronic neurological disease characterized by inflammation and degeneration within the central nervous system. Over the course of the disease, most MS patients successively accumulate inflammatory lesions, axonal damage, and diffuse CNS pathology, along with an increasing degree of motor disability. While the pharmacological approach to MS targets inflammation to decrease relapse rates and relieve symptoms, disease-modifying therapy and immunosuppressive medications may not prevent the accumulation of pathology in most patients leading to long-term motor disability.

Critical illness-associated weakness and related motor disorders.

Weakness of limb and respiratory muscles that occurs in the course of critical illness has become an increasingly common and serious complication of adult and pediatric intensive care unit patients and a cause of prolonged ventilatory support, morbidity, and prolonged hospitalization. Two motor disorders that occur singly or together, namely critical illness polyneuropathy and critical illness myopathy, cause weakness of limb and of breathing muscles, making it difficult to be weaned from ventilatory support, commencing rehabilitation, and extending the length of stay in the intensive care unit, with higher rates of morbidity and mortality. Recovery can take weeks or months and in severe cases, and may be incomplete or absent.

Adult and childhood vasculitis.

Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system leads to pervasive injury and disability, making this a disorder of paramount importance to all clinicians. There has been remarkable progress in the pathogenesis, diagnosis, and treatment of primary CNS and PNS vasculitides, predicated on achievement in primary systemic forms.

Autonomic failure: Clinicopathologic, physiologic, and genetic aspects.

Over the past century, generations of neuroscientists, pathologists, and clinicians have elucidated the underlying causes of autonomic failure found in neurodegenerative, inherited, and antibody-mediated autoimmune disorders, each with pathognomonic clinicopathologic features. Autonomic failure affects central autonomic nervous system components in the α-synucleinopathy, multiple system atrophy, characterized clinically by levodopa-unresponsive parkinsonism or cerebellar ataxia, and pathologically by argyrophilic glial cytoplasmic inclusions (GCIs). Two other central neurodegenerative disorders, pure autonomic failure characterized clinically by deficits in norepinephrine synthesis and release from peripheral sympathetic nerve terminals; and Parkinson's disease, with early and widespread autonomic deficits independent of the loss of striatal dopamine terminals, both express Lewy pathology.

Congenital myopathies.

The congenital myopathies are inherited muscle disorders characterized clinically by hypotonia and weakness, usually from birth, with a static or slowly progressive clinical course. Historically, the congenital myopathies have been classified according to major morphological features seen on muscle biopsy as nemaline myopathy, central core disease, centronuclear or myotubular myopathy, and congenital fiber type disproportion. However, in the past two decades, the genetic basis of these different forms of congenital myopathy has been further elucidated with the result being improved correlation with histological and genetic characteristics.

Childhood muscular dystrophies.

Infancy- and childhood-onset muscular dystrophies are associated with a characteristic distribution and progression of motor dysfunction. The underlying causes of progressive childhood muscular dystrophies are heterogeneous involving diverse genetic pathways and genes that encode proteins of the plasma membrane, extracellular matrix, sarcomere, and nuclear membrane components. The prototypical clinicopathological features in an affected child may be adequate to fully distinguish it from other likely diagnoses based on four common features: (1) weakness and wasting of pelvic-femoral and scapular muscles with involvement of heart muscle; (2) elevation of serum muscle enzymes in particular serum creatine kinase; (3) necrosis and regeneration of myofibers; and (4) molecular neurogenetic assessment particularly utilizing next-generation sequencing of the genome of the likeliest candidates genes in an index case or family proband.

Neonatal and infantile hypotonia.

The underlying etiology of neonatal and infantile hypotonia can be divided into primary peripheral and central nervous system and acquired or genetic disorders. The approach to identifying the likeliest cause of hypotonia begins with a bedside assessment followed by a careful review of the birth history and early development and family pedigree and obtaining available genetic studies and age- and disease-appropriate laboratory investigations. Until about a decade ago, the main goal was to identify the clinical signs and a battery of basic investigations including electrophysiology to confirm or exclude a given neuromuscular disorder, however the availability of whole-exome sequencing and next generation sequencing and transcriptome sequencing has simplified the identification of specific underlying genetic defect and improved the accuracy of diagnosis in many related Mendelian disorders.

On the path to evidence-based therapy in neuromuscular disorders.

Neuromuscular disorders encompass a diverse group of acquired and genetic diseases characterized by loss of motor functionality. Although cure is the goal, many therapeutic strategies have been envisioned and are being studied in randomized clinical trials and entered clinical practice. As in all scientific endeavors, the successful clinical translation depends on the quality and translatability of preclinical findings and on the predictive value and feasibility of the clinical models.

Neurogenetic motor disorders.

Advances in the field of neurogenetics have practical applications in rapid diagnosis on blood and body fluids to extract DNA, obviating the need for invasive investigations. The ability to obtain a presymptomatic diagnosis through genetic screening and biomarkers can be a guide to life-saving disease-modifying therapy or enzyme replacement therapy to compensate for the deficient disease-causing enzyme. The benefits of a comprehensive neurogenetic evaluation extend to family members in whom identification of the causal gene defect ensures carrier detection and at-risk counseling for future generations.

COVID-19 (novel SARS-CoV-2) neurological illness.

COVID-19 illness is associated with diverse neurological manifestations. Its exceptionally high prevalence results from unprecedented genetic diversity, genomic recombination, and superspreading. With each new mutation and variant, there are foreseeable risks of rising fatality and novel neurological motor complications in childhood and adult cases.