Multiple sclerosis natural history, complications and prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.

Multiple sclerosis usually start between age of fifteen to forty years, rarely before age fifteen or after age sixty with symptoms such as optic neuritis, diplopia, sensory or motor loss, vertigo and balance problems. It may be classified into four groups according to clinical course of the disease including relapsing-remitting, secondary-progressive, primary-progressive, and progressive-relapsing. Complications that can develop as a result of multiple sclerosis are: medication complication, Fatigue, mood problems, Spasticity, Bowel and bladder dysfunction, Cognitive impairment, Heat sensitivity., Incoordination, Pain, Sexual dysfunction, Sleep disorders, vertigo, visual loss. there are some factors associated with a particularly poor prognosis among patients with multiple sclerosis such as: Relapsing versus progressive disease, early symptoms, Demographics, Sex, Smoking.

• Multiple sclerosis usually start between age of fifteen to forty years, rarely before age fifteen or after age sixty with symptoms such as optic neuritis, diplopia, sensory or motor loss, vertigo, and balance problems. In young adult eye and sensory problems are prominent while in older patients we see motor problems more often.^[1]
• The natural history of the disease is either relapsing or progressive.
• Relapsing-remitting multiple sclerosis is defined by acute attacks of neurological dysfunction followed by full or partial recovery. Patient clinical symptoms are stable between the attacks.
• It can switch to secondary progressive disease when the neurological symptoms progressively worsen between the attacks.
• There is also primary progressive type, which is defined by continuously worsening of neurological dysfunction with no distinct attacks and remissions.
• Progressive relapsing type is a mixture of relapsing and progression and is defined by progression of disease from the beginning with acute attack episodes.^[2]
• The most common symptoms in all of the MS patients are fatigue, mood problems, spasticity, bowel and bladder dysfunction, cognitive impairment, eye movement abnormalities, heat sensitivity, incoordination , pain, sexual dysfunction, sleep disorders, vertigo, and visual loss.^{[3][4][5][6][7][8][9][10][11][12][13][14][15]}

Complications that can develop as a result of mutiple sclerosis include:

• Medication complications: Insufficient blood supply to the bone can cause avascular osteonecrosis. After trauma, corticosteroid treatment is the most common cause of AVN.^[16][17]

• Fatigue: Fatigue is seen in almost 80% of MS patients. They commonly feel exhausted and out of energy. We can see fatigue exacerbation before acute attacks in MS and for a while after that.^[18]

• Mood problems: Psychiatric disorders especially depression is common and can be seen in almost 50% of MS patients.^[5] Some studies show higher risk of suicide in MS patient.^[19][20]

• Spasticity: Damage to the upper motor neurons and decrease inhibition of lower motor neurons in MS can increase muscle tone and rigidity in 75% of MS patients.^[6]

• Bowel and bladder dysfunction: Bowel and bladder dysfunction is common in MS patients and occurs in more than 50% of cases.^[7] bladder dysfunction can be the result of Detrusor overactivity, Detrusor sphincter dyssynergia, Inefficient bladder contractility and Abnormal sensation and bladder hypoactivity.^[21] the most common bowel problems include Constipation, poor defecation and incontinence.^[22]

• Cognitive impairment: Cognitive disorders is common in MS patients and can even present at early stages of disease. These disorders are in attention, short term memory, and information processing. Relapsing-remitting type of MS seems to have a lower cognitive problems.^{[8][23][24][25]}

• Heat sensitivity: Patients with MS disease are more sensitive to heat. A slight increase in body temperature of these patients will lead to worsening of their signs and symptoms.^[10]
• Incoordination: Involvement of cerebellar tracts can cause problems in Gait and balance, poor coordinated actions, and slurred speech. Intention tremor is present in most of these patients.^[11]

• Pain: Pain is a very common symptom in MS. Patients can be either from neurogenic source leading to burning or ice-cold dysesthesias or from long immobilization and spasm.^[12][26]

• Sexual dysfunction: Sexual dysfunction can be due to involvement of motor and sensory pathways or from psychological problems. Either way, it’s a very common symptom. In women, we can see reduced libido and orgasm, dyspareunia and decrease vaginal sensation. Presentations of sexual dysfunction in men are decreased libido and premature ejaculation, erectile dysfunction and decreased penile sensation.^[13][27]

• Sleep disorders: Many patients with multiple sclerosis suffer from sleep disorders and daytime somnolence. This can be the result of so many conditions including restless leg syndrome, nocturia, pain, and medication side effects. Having more cervical lesions lead to experiencing restless leg syndrome more often.^[14][28][29]

• Vertigo: Benign positional paroxysmal vertigo is the most common cause of vertigo in an MS patient. In the course of the disease about 30-50% of patients experience this symptom.^[15]

• Visual loss: Optic neuritis is the most common eye involvement and presents as an acute unilateral eye pain, followed by some degree of vision loss.^[3]

There are some factors associated with a particularly poor prognosis among patients with multiple sclerosis. However, we can’t surly say what is the prognosis of MS patients.^[30]

• Relapsing versus progressive disease: Progressive form of MS seems to have a worse prognosis in comparison to relapsing remitting form of MS. Disabilities start sooner in progressive form^[31][32][33] but some studies showed that age of onset is more important in MS disability than the form of the disease.^[34][35]

• Early symptoms: Some first manifestations of MS disease like bowel and bladder dysfunction seem to have a worse prognosis.^[36]. Another study demonstrated that having so many symptoms at the onset of the disease have a worse prognosis than being monosymptom.^[37]

• Demographics: Onset of MS in Black Americans is in later age and they are more susceptible of having multifocal signs and symptoms and involvement of optic nerve and spinal cord.^[38]

• Sex: Women seems to have younger age of onset and so better prognosis than men.^[31]

• Smoking: Transition of RRMS to SPMS can be accelerated with smoking.^[39]

• Lipid specific immunoglobulin level: Lipid specific immunoglobulin level in CSF can predict long term outcomes of MS disease.^[40]

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