Multiple sclerosis (MS)

● an idiopathic demyelinating disease of the CNS producing exacerbating and remitting symptoms disseminated in space and time

● classic clinical findings: optic neuritis, paresthesias, INO and bladder symptoms

● diagnostic criteria (McDonald criteria) use clinical and/or lab results (MRI, CSF…) to stratify patients as: MS, probable MS, or not MS

● MRI: multiple usually enhancing lesions involving optic nerves & white matter of brain (especially periventricular white matter), cerebellum and spinal cord

An idiopathic demyelinating disease (thus affecting only white matter) of the cerebrum, optic nerves, and spinal cord (especially the corticospinal tracts and the posterior columns). It does not affect peripheral myelin. Pathologically produces multiple plaques of various ages in diffuse locations in the CNS, especially in the periventricular white matter. Lesions initially evoke an inflammatory response with monocytes and lymphocytic perivascular cuffing, but with age settle down to glial scars.

Multiple sclerosis (MS) is characterized by widespread immunomodulatory demyelination of the CNS resulting in nerve cell dysfunction.

The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis.

Abdominal reflexes disappear in 70-80 %.

Cell replacement therapy is an effective strategy to repair the myelin in MS.

Multiple sclerosis epidemiology.

Multiple sclerosis classification.

classic clinical findings: optic neuritis, paresthesias, INO and bladder symptoms

Disturbances of visual acuity may be caused by optic or retrobulbar neuritis which is the presenting symptom of MS in 15% of cases, and which occurs at some time in 50% of MS patients. The percentage of patients with an attack of optic neuritis and no prior attack that will go on to develop MS ranges from 17–87%, depending on the series 1). Symptoms: acute visual loss in one or both eyes with mild pain (often on eye movement).

Diplopia may be due to internuclear ophthalmoplegia (INO) from a plaque in the MLF. INO is an important sign because it rarely occurs in other conditions besides MS or brainstem stroke.

50–90% of patients develop voiding symptoms at some point. The demyelination primarily involves the posterior and lateral columns of the cervical spinal cord. Detrusor hyperreflexia is the most common urodynamic abnormality (in 50–99% of cases), with bladder areflexia being less common (5–20%). Patients have DO with DSD without upper tract injury or loss of compliance.

Extremity weakness (mono, para, or quadriparesis) and gait ataxia are among the most common symptoms of MS. Spasticity of the LEs is often due to pyramidal tract involvement. Scanning speech results from cerebellar lesions.

Posterior column involvement often causes loss of proprioception. Paresthesias of extremities, trunk, or face occur. Lhermitte Sign (electric shock-like pain radiating down the spine on neck flexion) is common, but is not pathognomonic. Trigeminal neuralgia occurs in ≈ 2%, and is more often bilateral and occurs at a younger age than the population in general.

Euphoria (la belle indifference) and depression occur in ≈ 50% of patients. Reflex changes Hyperreflexia and Babinski signs are common. Abdominal cutaneous reflexes disappear in 70–80%. GU symptoms Urinary frequency, urgency, and incontinence are common. Impotence in males and reduced libido in either sex is often seen.

The limited efficacy of immunomodulatory treatments (e.g. interferons) for MS, means that more rational, if not, better approaches in the treatment of MS have been sought, such as enhancement of neuroregeneration (e.g. remyelination) via stem cell transplantation. Oligodendrocytes are a good stem cell source because lineage differentiation of these cells is primarily altered in MS (20,32). Moreover, we hypothesize that transplanting BMDOs loaded with Ephrin (BMDO+Ephrin) may increase migratory capacity of these grafts and eventually promote remyelination, behavioral recovery and improvement of motor functions in MS animals. Of course, several issues remain to be addressed prior to establishing the optimal efficacy of BMDO+Ephrin transplantation in MS animal models. For instance, timing of transplantation after EAE induction is critical for successful functional outcomes. Therefore, early transplantation post- immunization should be performed, especially for chronic EAE. Furthermore, aside from looking into remyelination in white matter tracts of the cerebral hemispheres after BMDO+Ephrin transplantation in animal models of MS, we also need to characterize the effects of these transplants in the spinal cord. It would also be worthwhile to explore other proteins aside from ephrin (e.g. syndecans) that could enhance migration of transplanted oligodendrocytes 2).

Multiple sclerosis related trigeminal neuralgia.

The diagnosis of a brain tumor in a MS patient is challenging, due to several reasons that include the fact that new neurological symptoms in MS patients are easily attributed to a relapse of the disease and the MRI lesions, even if suspicious, are commonly diagnosed or confused as a tumefactive form of MS. Also the cooccurrence of two neurological diseases in the same patient is uncommon, particularly oligodendroglioma and MS 3) 4) 5) 6).

Cervical spinal stenosis (CS) and multiple sclerosis (MS) are two common conditions with distinctive pathophysiology but overlapping clinical manifestations. The uncertainty involved in attributing worsening symptoms to CS in patients with MS due to extremely high prevalence of asymptomatic radiological CS makes treatment decisions challenging. A retrospective review was performed analyzing the medical records of all patients with confirmed diagnosis of MS who had coexistent CS and underwent surgery for cervical radiculopathy/myeloradiculopathy. Eighteen patients with coexistent CS and MS who had undergone cervical spine decompression and fusion were identified. There were six men and 12 women with an average age of 52.7years (range 40-72years). Pre-operative symptoms included progressive myelopathy (14 patients), neck pain (seven patients), radiculopathy (five patients), and bladder dysfunction (seven patients). Thirteen of the 14 patients (92.9%) with myelopathy showed either improvement (4/14, 28.6%) or stabilization (9/14, 64.3%) in their symptoms with neck pain and radiculopathy improving in 100% and 80% of patients, respectively. None of the seven patients with urinary dysfunction had improvement in urinary symptoms after surgery.

Cervical spine decompression and fusion can improve or stabilize myelopathy, and significantly relieve neck pain and radiculopathy in the majority of patients with coexistent CS and MS. Urinary dysfunctions appear unlikely to improve after surgery. The low rate of surgical complications in this cohort demonstrates that cervical spine surgery can be safely performed in carefully selected patients with concomitant CS and MS with a good clinical outcome and also eliminate CS as a confounding factor in the long-term management of MS patients 7).

see Multiple sclerosis diagnosis.

The plethora of possible signs and symptoms in MS causes the differential diagnosis to extend to almost all conditions causing focal or diffuse dysfunction of the CNS. Conditions

that may closely mimic MS clinically and on diagnostic testing include:

1. acute disseminated encephalomyelitis (ADEM): generally monophasic. May also have CSF-OCB. Corpus callosum involvement is uncommon

2. CNS lymphoma

3. other closely related demyelinating diseases: e.g. Devic syndrome

4. vasculitis

5. encephalitis: patients are usually very ill

6. chronic white matter changes: seen in older patients.

Differentiating neuromyelitis optica spectrum disorder (NMOSD) and Myelin oligodendrocyte glycoprotein antibody disorder (MOG-AD) from multiple sclerosis (MS) is important since MS therapies might result in progression and relapse of the former diseases. Evidence of long extending transverse myelitis (LETM) in magnetic resonance imaging (MRI) is one of the requirements to make an NMOSD diagnosis. However, centrally located lesions on spinal MRI may bring higher sensitivity and specificity to the NMOSD and MOG-AD diagnosis. Diagnostic criteria including the centrality, location, and expansion of the transverse myelitis lesions, in addition to LETM, may be more accurate in the diagnosis of NMOSD and MOG-AD and their distinction from MS 8).

see Multiple sclerosis treatment.

Quality of life, in patients with multiple sclerosis is an issue that worries health personnel, it is essential to implement strategies for reducing the impact of the disease on patients' lives, mainly through the application of programs aimed to decrees depression and improve social support 9).

Multiple sclerosis case series.

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Etemadifar M, Salari M, Etemadifar MR, Sabeti F, Fateh ST, Aminzade Z. Centrally-located transverse myelitis would facilitate the differentiation of NMOSD and MOG-AD from MS. Mult Scler Relat Disord. 2022 Feb 12;60:103664. doi: 10.1016/j.msard.2022.103664. Epub ahead of print. PMID: 35219242.
Ochoa-Morales A, Hernández-Mojica T, Paz-Rodríguez F, Jara-Prado A, Trujillo-De Los Santos Z, Sánchez-Guzmán MA, Guerrero-Camacho JL, Corona-Vázquez T, Flores J, Camacho-Molina A, Rivas-Alonso V, Dávila-Ortiz de Montellano DJ. Quality of life in patients with multiple sclerosis and its association with depressive symptoms and physical disability. Mult Scler Relat Disord. 2019 Sep 9;36:101386. doi: 10.1016/j.msard.2019.101386. [Epub ahead of print] PubMed PMID: 31520986.
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