Clinical Presentation of MS1016

O MS symptoms are a function of the location of lesions within the CNS. Because myelin increases the speed of nerve impulse transmission, demyelination slows the speed of transmission. No impulses can be transmitted if the axon is transected. The primary symptoms of MS are caused by this delay or cessation of impulses. Secondary symptoms of MS result from the primary symptoms.

Primary Symptomi

Frequency of Ouuiitiui (it)

Related ietonddry Symplomi

Urinary Symptom;. IjK Ora iriCrXfl Urinary retention

Soawiciiy visual symptoms Optic neuritis

Diplopia Rowel syrnplcmi ircomtinence ConMipdlion E>e passion Gogniii^ deficits Weakness Fatigue

Ubthoff's phciwmcnor Sexual dysfunction Erectilc dysfunction Fccnalc sexual -dyfsruriciion Tremor Pain

Trigeminal neuralgia j.lier in ¡lie's sign Oywsthedc [win

60 ss

29-51 35-54 SO SO

76-92 80

70 72 25

Decubitus lcIl e-rs

Urinary [rJCl iiifeciiOrti

Fjiis, care difficulties, pair*. gais problems

FjBs. care difficulties

Pcciibiiui us«rs

Pair

Suidde tare difficulties faHs, care difficulties* gait probiems

IV adrenocorticotropic hormone, IV methylprednisolone, or oral prednisone hasten functional recovery after relapses.26 Traditionally, IV methylprednisolone was the drug of choice for acute relapses because an optic neuritis study demonstrated re-

27 28

duced recurrence with IV methylprednisolone, but not oral prednisone. ' More recent studies show equal efficacy of equivalent doses of IV and oral dosage forms, and oral dosing avoids discomfort, inconvenience, and expense of IV therapy.29,30

Adverse Effects

Short-term corticosteroid use is not associated with most of the adverse effects of chronic steroid use. The most common adverse effects are GI upset, insomnia, and

mood swings.

Dosing and Administration

Methylprednisolone is given 1 g/day IV as one dose or in divided doses for 3 to 5 days. Oral prednisone 1,250 mg/day given every other day for five doses provides an equivalent dose.

Clinical improvement usually begins during corticosteroid treatment. Neurologic

recovery is equivalent with or without a subsequent oral prednisone taper.

Outcome Evaluation

• Monitor for improvement of symptoms

• Educate regarding adverse effects and reporting directions

Disease-Modifying Therapies

Six agents are indicated for MS: subcutaneous interferon P-1a (Rebif); intramuscular interferon P-1a (Avonex); interferon P-1b (Betaseron); glatiramer acetate (Copaxone); mitoxantrone (Novantrone); and natalizumab (Tysabri). A broad look across all stud-

ies of these immunomodulators shows about 30% relapse reduction. P-Interferons

Pharmacology and Mechanism of Action. The mechanism of action of P-interferons is incompletely understood. The following properties are thought to be important:

• Decrease in T-cell activation, decreasing cytokine secretion and preserving myelin

• Prevention of upregulation of adhesion molecules on activated T cells, limiting the number of T cells that can get into the brain

• Suppression of MMPs, maintaining the integrity of the blood-brain barrier

FIGURE 29-2. McDonald diagnostic criteria for MS.17-19 MRI evidence of dissemination over time is a gadolinium-enhancing lesion on an MRI done at least 3 months following onset of clinical attack at a site different from the initial attack, or a gadolinium-enhancing lesion or new T2-weighted lesion 6 months following onset of clinical attack. Positive CSF is oligoclonal immunoglobulin G bands in CSF but not serum or elevated immunoglobulin G index. Positive evoked potentials are delayed, but maintain a well-preserved waveform. (CSF, cerebrospinal fluid.)

FIGURE 29-2. McDonald diagnostic criteria for MS.17-19 MRI evidence of dissemination over time is a gadolinium-enhancing lesion on an MRI done at least 3 months following onset of clinical attack at a site different from the initial attack, or a gadolinium-enhancing lesion or new T2-weighted lesion 6 months following onset of clinical attack. Positive CSF is oligoclonal immunoglobulin G bands in CSF but not serum or elevated immunoglobulin G index. Positive evoked potentials are delayed, but maintain a well-preserved waveform. (CSF, cerebrospinal fluid.)

• Dissemination in space by MRI evidence of nine or more T2-weighted brain lesions, or two or more cord lesions, or four to eight brain and one cord lesion, or positive visual evoked potentials with four to eight MRI lesions, or positive visual evoked potentials with less than four brain lesions plus one cord lesion.

• Decrease in microglial proliferation, preserving myelin

• Promotion of formation of Th2 cells rather than Th1 cells, decreasing inflammation

8 33

• Inhibition of viruses, important if MS has a viral etiology ' Efficacy

Patients With Relapsing Remitting MS. A meta analysis of all ^-interferons determined that treated patients were 27% and 19% less likely to have a relapse during the first and second years of treatment, respectively, compared to placebo.34 Early treatment after a first clinical attack delayed time to a second attack by 9 to 13 months o c -3 /:

compared to placebo. , Treating early is also associated with a lower incidence of developing clinically definite MS compared to delaying treatment.37,38

Patients With Secondary Progressive Ms Who Experience Relapses. ^-Interferons have mixed results for slowing disease progression in secondary progressive MS.

Treatment is most likely to be effective if clinical relapses or MRI signs of inflammat-

ory activity are present.

Adverse Effects. Adverse effects are common with the ^-interferons (Table 29-3). Flu-like symptoms include fever, fatigue, muscle aches, malaise, and chills. Symptoms begin a few hours postinjection and dissipate within 8 to 24 hours.40 Preventive measures can be employed (Table 29-4). In temperature-sensitive patients, ^-interfer-on-induced fever can transiently worsen MS symptoms. Injection site reactions range from redness to necrosis. There are preventive and treatment measures for these reactions (Table 29-4). At the threshold laboratory values (Table 29-4), interferon should be suspended. When values normalize, interferon is resumed with gradual dose increases and careful monitoring40a-and y-interferons are associated with depression. Up to 50% of MS patients experience depression, even without P-interferon treatment.14 Because of conflicting data, it is difficult to determine whether ^-interferons cause or worsen MS-related depression.14

FIGURE 29-3. Comparison of clinical course of MS by type. Table 29-2 Clinical Rating Scales Used in MS

EDSS

Rates functional systems from 0 (normal) to 10 (death due to MS) Emphasis is on ambulation over other symptoms

MSFC

Three-part tool rating ambulation, limb function, and cognitive function Composite score is compared to standardized population Correlates better with MRI data than EDSS

MS, multiple sclerosis; EDSS, Expanded Disability Status Scale; MSFC, multiple sclerosis functional composite.

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