Best Dx/Best Rx: Hypertension

From: Subject: Best Dx/Best Rx: Hypertension Date: Wed, 3 Jun 2009 21:58:10 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_029B_01C9E496.62693860" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_029B_01C9E496.62693860 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx1109.htm Best Dx/Best Rx: Hypertension

Demyelinating=20 Diseases

Multi= ple=20 Sclerosis
Optic= =20 Neuritis
Acute= =20 Disseminated Encephalomyelitis
Trans= verse=20 Myelitis
Inher= ited=20 Demyelinating Diseases
Metab= olic=20 Demyelinating Diseases
Virus= -Induced=20 Demyelination

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Multiple = Sclerosis

J. William Lindsey, M.D.
Jerry S. Wolinsky, M.D.
University = of=20 Texas Health Science Center at Houston

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Recurrent or chronically = progressive=20 neurologic dysfunction caused by lesions in the CNS
Lesions are multiple areas = of=20 demyelination that develop in the brain, optic nerves, and spinal cord =
Affects women more than men=20 (2:1)=20
More common in whites than = in blacks;=20 rare in Asians
Onset at 20=9650 yr of age, = peak at 30=20 yr of age=20
Highest prevalence at higher = latitudes=20
Susceptibility is at least = partly=20 familial
Optic neuritis
- Usually unilateral
- Central scotoma
- Retro-orbital pain
- Develops over several days =
Diplopia=20
Sensitivity to heat; symptoms resolve when body temperature = returns to=20 normal=20
Lhermitte symptom: paresthesias that radiate down the spine and = into the=20 extremities on neck flexion; indicates a lesion in the cervical spine=20
Weakness of the upper motor neuron type=20
- Accompanied by spasticity and increased reflexes=20
- May be paraparesis, hemiparesis, or monoparesis
Paresthesias or loss of sensation (most often loss of vibration = sense)=20
Lower extremities more severely affected=20
Ataxia=20
Bladder control problems=20
Constipation=20
Progressive or relapsing-remitting pattern=20
Permanent neurologic deficits develop with repeated exacerbations=20

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Differential=20 Diagnosis

Structural lesions=20
Inherited demyelinating or degenerative diseases=20
Vasculitides=20
Vascular disease=20
Chronic infections (e.g., syphilis, Lyme disease, and human T cell = lymphotropic virus type I)=20
Vitamin B₁₂ deficiency=20
Neurosarcoidosis

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Best=20 Tests

Optical examination=20
- Fundus usually normal=20
- Papillitis or pallor of the disk may be present=20
- Failure of adduction on lateral gaze but preservation of = adduction with=20 convergence
MRI=20
- Sensitive but not specific findings supportive of MS include the = following:=20
  - ≥ 3 white-matter lesions=20
  - Lesions abutting the body of the lateral ventricles=20
  - Juxtacortical lesions=20
  - Infratentorial lesions=20
  - Lesions > 5 mm=20
  - Lesions that show gadolinium enhancement
- Lesions are hyperintense on T₂-weighted or = proton-density=20 imaging and are hypointense or isointense on T₁-weighted = imaging=20
- Typical lesions are ovoid and periventricular, with their long = axis=20 perpendicular to the ventricle, but they may appear anywhere in the = white=20 matter=20
- Cerebral atrophy is often present and increases over time =
CSF analysis=20
- Comparative electrophoresis of serum and concentrated CSF=20
- Shows oligoclonal immunoglobulin bands=20
- For optimal sensitivity, the paired samples should be analyzed = with=20 isoelectric focusing followed by immunofixation=20
- Quantitative measures of immunoglobulin content, such as the IgG = index=20 and the rate of IgG synthesis
Summated cortical evoked response=20
- Measures conduction along visual, auditory, and somatosensory = pathways=20
- Slowing of conduction indicates demyelination=20
- Confirms demyelination in a particular sensory pathway in the = absence of=20 signs or symptoms=20
- Visual evoked responses are most useful =

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Best Therapy

Management of Acute Relapse

High-dose corticosteroid therapy=20
- Contraindications: type 1 diabetes mellitus, uncontrolled = hypertension,=20 prior steroid-induced depression or psychoses=20
- Methylprednisolone=20
  - Dose: 0.5=961.0 g/day I.V. for 3=967 days=20
  - Oral corticosteroids may follow methylprednisolone; taper over = 1=962 wk=20 starting with prednisone, 60 mg/day
Early start of rehabilitation therapy to counteract reduced = physical=20 activity during exacerbation

Prevention of Relapse

The following agents can reduce the frequency of attacks, reduce = the rate=20 of MS lesion accumulation on MRI, and reduce the accumulation of = disability:=20
- Interferon beta-1b: for patients with relapsing disease of mild = to=20 moderate severity=20
  - Dose: 0.25 mg (8 million IU) S.C. q.o.d.=20
  - Side effects=20
    - Flulike symptoms, which can be controlled with prior = administration=20 of an NSAID=20
    - Injection-site skin necrosis=20
    - Elevation of liver enzymes=20
    - Leukopenia
- Interferon beta-1a=20
  - Avonex=20
    - Dose: 30 =B5g I.M. once a week=20
    - Cost/mo: $1,195
  - Rebif=20
    - Dose: 44 =B5g S.C. three times a week=20
    - Cost/mo: $1,400
  - Side effects=20
    - Flulike symptoms, which can be controlled with prior = administration=20 of an NSAID=20
    - Injection-site skin necrosis=20
    - Elevation of liver enzymes=20
    - Leukopenia
- Glatiramer acetate=20
  - Dose: 20 mg S.C. q.d.=20
  - Side effects=20
    - Injection-site reactions=20
    - Infrequent postinjection syndrome=20
    - Cost/mo: $1,176

Progressive MS

Interferons and glatiramer acetate not effective=20
Mitoxantrone: effective for selected patients with very active = disease;=20 significant side effects=20
- Dose: 12 mg/m² of mitoxantrone given every 3 mo for 2 = yr=20
- Side effects: nausea, hair loss, menstrual irregularities, = infections;=20 cardiotoxic at higher doses

Symptomatic Therapy

Depression

Treatment as for others with depression

Fatigue

Amantadine: effective for ~ 50% of patients with MS=20
- Dose: 100 mg b.i.d. or t.i.d=20
- Cost/mo: $24=20
- Avoid dosing late in the day, which may induce insomnia =
Modafanil=20
- Dose: 100 mg b.i.d.=20
- Cost/mo: $285
Methylphenidate=20
- Dose: 10 mg b.i.d. to 20 mg t.i.d.

Spasticity

Baclofen=20
- Dose: 5 mg t.i.d. to 20 mg q.i.d=20
- Cost/mo: $40
Clonidine (adjunctive to baclofen)=20
- Dose: 0.1. mg b.i.d. to 0.2 mg t.i.d=20
- Cost/mo: $12
Diazepam=20
- Dose: 2 mg t.i.d. to 10 mg q.i.d=20
- Cost/mo: $20
Tizanidine=20
- Dose: 4 mg q.d. to 12 mg q.i.d=20
- Cost/mo: $307
Clonazepam=20
- Dose: 0.5 mg t.i.d. to 5 mg q.i.d=20
- Cost/mo: $144
Dantrolene=20
- Dose: 25 mg q.d. to 100 mg q.i.d=20
- Cost/mo: $187
Intrathecal baclofen or selective botulinum toxin injections for = selected=20 patients with severe spasticity that is unresponsive to oral treatment =

Ataxia

Clonazepam=20
- Dose: 0.5 mg t.i.d. to 5 mg q.i.d.=20
- Cost/mo: $144
Gabapentin=20
- Dose: 100=96600 mg t.i.d.=20
- Cost/mo: $90

Bladder Urgency

Oxybutynin=20
- Dose: 5 mg b.i.d. to q.i.d.=20
- Cost/mo: $26
Tolterodine=20
- Dose: 2 mg b.i.d.=20
- Cost/mo: $96
Imipramine=20
- Dose: 25=9675 mg q.h.s.=20
- Cost/mo: $27
Hyoscyamine=20
- Dose: 0.125 mg b.i.d. to 0.25 mg q.i.d.=20
- Cost/mo: $34
Propantheline=20
- Dose: 7.5 mg t.i.d. to 15 mg q.i.d.=20
- Cost/mo: $51

Bladder Dyssynergia

Phenoxybenzamine=20
- Dose: 10 mg b.i.d. to 20 mg t.i.d.=20
- Cost/mo: $1,050
Clonidine=20
- Dose: 0.1 mg b.i.d. to 0.2 mg t.i.d.=20
- Cost/mo: $12
Terazosin=20
- Dose: 1=965 mg q.d.=20
- Cost/mo: $14

Bladder Retention=20

Bethanechol=20
- Dose: 10 mg t.i.d. to 50 mg q.i.d.=20
- Cost/mo: $240
Intermittent self-catheterization ≥ q.i.d.

Paroxysmal Pain

Analgesics=20
Carbamazepine=20
- Dose: 100=96300 mg t.i.d.=20
- Cost/mo: $47
Phenytoin=20
- Dose: 300=96400 mg q.d.=20
- Cost/mo: $36

Trigeminal Neuralgia

Misoprostol=20
- Dose: 100=96200 =B5g q.i.d.=20
- Cost/mo: $114

Dysesthetic Pain

Amitriptyline=20
- Dose: 50=96150 mg q.h.s.=20
- Cost/mo: $3
Phenytoin=20
- Dose: 300=96400 mg q.d.=20
- Cost/mo: $36
Gabapentin=20
- Dose: 100=96600 mg t.i.d.=20
- Cost/mo: $90
Valproic acid=20
- Dose: 250=961,000 mg t.i.d.=20
- Cost/mo: $108

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Best References

Lublin FD, et al: Neurology 46:12, 1996

McDonald WI, et al: Ann Neurol 50:121, 2001

Milligan NM, et al: J Neurol Neurosurg Psychiatry 50:511, 1987

Noseworthy JN, et al: N Engl J Med 343:938, 2000

Wolinsky JS: Expert Opin Pharmacother 5:875, 2004

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Optic Neuritis

J. William Lindsey, M.D.
Jerry S. Wolinsky, M.D.
University = of=20 Texas Health Science Center at Houston

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Acute inflammatory optic neuropathy=20
Unilateral vision loss=20
Retrobulbar pain with eye movement

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Differential=20 Diagnosis

Anterior ischemic optic neuropathy=20
Hereditary diseases (e.g., Leber hereditary optic neuropathy)=20
Toxic or nutritional optic neuropathies=20
More than half of all MS patients have optic neuritis at some time =

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Best=20 Tests

Brain MRI: shows one or more ovoid or periventricular lesions in ~ = 40% of=20 patients=20
CSF evaluation

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Best Therapy

Methylprednisolone: hastens recovery of vision but has little = residual=20 benefit at 1 yr=20
- Dose: 1 g/day I.V. for 3 days followed by oral prednisone = starting at 60=20 mg/day and tapering over 11 days
Even without treatment, almost all patients begin to recover = vision within=20 4 wk

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Best References

Beck RW, et al: N Engl J Med 326:581, 1992

Newman NJ: Neurology 46:315, 1996

Rodriguez M, et al: Neurology 45:244, 1995

Soederstroem M, et al: Neurology 50:708, 1998

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Acute Disseminated Encephalomyelitis

J. William Lindsey, M.D.
Jerry S. Wolinsky, M.D.
University = of=20 Texas Health Science Center at Houston

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Usually preceded by a viral = exanthem,=20 an upper respiratory infection, or vaccination
Most commonly associated = with measles,=20 paramyxovirus, varicella, rubella, and Epstein-Barr virus
Rapid onset
Meningeal signs, headache, = seizures,=20 altered mental status
Variable neurologic = deficits,=20 including hemiplegia, paraplegia, sensory loss, vision loss, and = transverse=20 myelitis
Can be fatal, but most = patients begin=20 to recover within 2=964 wk

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Differential=20 Diagnosis

Multiple sclerosis=20
Viral encephalomyelitis=20
Inherited leukodystrophies

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Best Tests

MRI: shows multiple white-matter lesions

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Best Therapy

Corticosteroids: efficacy not proven=20
Plasmapheresis

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Best References

Lin CH, et al: J Clin Apheresis 19:154, 2004

Mader I, et al: AJNR Am J Neuroradiol 17:104, 1996

Tenembaum S, et al: Neurology 59:1224, 2002

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Transverse Myelitis

J. William Lindsey, M.D.
Jerry S. Wolinsky, M.D.
University = of=20 Texas Health Science Center at Houston

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Syndrome of spinal cord = dysfunction=20
Thoracic cord is most often = affected=20
Rapid onset
May follow infection or = vaccination=20
May be initial presentation = of MS=20
Paraparesis, initially = flaccid and=20 then spastic
Loss of sensation with a = sensory level=20 on the trunk
Bowel and bladder = dysfunction
Back pain precedes the = neurologic=20 symptoms, and the sensory symptoms may begin distally and ascend =
One third of patients have = good=20 outcome, one third have fair outcome, one third do not recover
Spinal shock, back pain, and = catastrophic onset are associated with poor outcome

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Differential=20 Diagnosis

Extradural structural lesion=20
Neoplasms=20
Ischemia=20
Systemic lupus erythematosus

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Best=20 Tests

MRI=20
- To exclude structural lesions=20
- To confirm intramedullary lesion commensurate with symptoms=20
- Lesions typically hyperintense on T₂-weighted = imaging,=20 involve most of the cross-sectional area of the cord over several = segments,=20 may be enhanced with contrast=20
- Lesions may cause spinal cord swelling

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Best Therapy

Usually treated with I.V. methylprednisolone, 1,000 mg/day for 5 = days, but=20 there are no controlled trials

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Best References

Choi KH, et al: AJNR Am J Neuroradiol 17:1151, 1996

Christensen PB, et al: Acta Neurol Scand 81:431, 1990

Tartaglino LM, et al: Radiology 201:661, 1996

Transverse Myelitis Consortium Working Group: Neurology 59:499,=20 2002

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Inherited Demyelinating Diseases

J. William Lindsey, M.D.
Jerry S. Wolinsky, M.D.
University = of=20 Texas Health Science Center at Houston

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Adrenoleukodystrophy

Associated with progressive=20 demyelination and dysfunction of the adrenal cortex
Accumulation of very long = chain fatty=20 acids (VLCFAs)=20
Autosomal recessive or = X-linked=20 recessive=20
Phenotypes vary considerably =
Childhood form
- Presents with cognitive = deficits and=20 rapid neurologic deterioration
- Death occurs in 2=965 yr=20
Adult form (adrenomyeloneuropathy)=20
- Mean age at onset is 28 yr=20
- Progressive spinal cord dysfunction=20
- Spastic paraparesis=20
- Sensory loss=20
- Bowel and bladder symptoms=20
- Rapidly progressive cerebral lesions 5=9610 yr after onset of = spinal cord=20 symptoms=20
- Cerebral involvement may be minimal

Metachromatic Leukodystrophy =

Demyelination of axons in the central and peripheral nervous = systems=20
Autosomal recessive=20
Onset in infancy or childhood, rarely in adulthood=20
Earlier onset associated with more rapid progression=20
Mean survival in adult-onset disease is 12 yr=20
Symptoms of adult-onset disease:=20
- Progressive behavioral abnormalities=20
- Dementia=20
- Ataxia=20
- Neuropathy

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Differential=20 Diagnosis

Adrenoleukodystrophy=20
Metachromatic leukodystrophy=20
Krabbe syndrome=20
Pelizaeus-Merzbacher syndrome

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Best=20 Tests

Adrenoleukodystrophy =

MRI=20
- Only half of adult-onset patients have brain abnormalities, most = often=20 in the corticospinal tracts=20
- Most patients have diffuse atrophy of the spinal cord
Family history=20
Serum VLCFA: elevated

Metachromatic Leukodystrophy =

MRI or CT of the brain=20
- Atrophy=20
- Diffuse white-matter abnormalities, particularly in the frontal = lobes=20
Arylsulfatase A activity in peripheral blood leukocytes, urine, or = skin=20 fibroblasts

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Best Therapy

Adrenoleukodystrophy

Dietary treatment with unsaturated fatty acids=20
- Lowers level of VLCFAs=20
- Does not significantly affect the progression of symptoms =
Bone marrow transplantation=20
- May be effective if performed before severe symptoms develop=20

Metachromatic Leukodystrophy

No effective therapy

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Best References

Aubourg P, et al: N Engl J Med 329:745, 1993

Eichler FS, et al: Neurology 58:901, 2002

Hageman AT, et al: Arch Neurol 52:408, 1995

Kumar AJ, et al: AJNR Am J Neuroradiol 16:1227, 1995

Moser HW: J Neuropathol Exp Neurol 54:740, 1995

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Metabolic Demyelinating Diseases

J. William Lindsey, M.D.
Jerry S. Wolinsky, M.D.
University = of=20 Texas Health Science Center at Houston

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Central=20 Pontine Myelinolysis

Neurologic deficits = occurring after=20 rapid correction of hyponatremia (faster than 10=9612 mEq/L in 24 = hr)=20
Usually occurs in young to = middle-aged=20 adults
Associated with alcohol = abuse or=20 malnutrition
Signs and symptoms
- Usually begin 3 days after = the start=20 of sodium replacement
- Changes in mental status =
- Dysarthria and other signs = of=20 corticobulbar dysfunction
- Spastic quadriplegia =
Improvement usually begins ~ 2 wk after onset of symptoms, but = degree of=20 recovery is variable=20
May also occur after liver transplantation

Vitamin=20 B₁₂ Deficiency=20

Causes demyelination of axons in the central and peripheral = nervous=20 systems=20
Paresthesias=20
Sensory loss beginning in the feet and progressing proximally=20
Weakness beginning after sensory loss=20
Sensory ataxia=20
Memory difficulties, irritability, and confusion in some patients =

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Differential=20 Diagnosis

Central Pontine Myelinolysis

Pontine infarct=20
Brainstem encephalitis=20
Multiple sclerosis

Vitamin B₁₂ = Deficiency=20

Nitrous oxide exposure

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Best=20 Tests

Central Pontine Myelinolysis

T₂-weighted MRI: usually shows hyperintense lesions = that=20 usually do not enhance with contrast

Vitamin = B₁₂=20 Deficiency=20

Physical examination=20
- Decreased vibration and position sense, worse in the feet than = in the=20 hands=20
- Spastic paraparesis
Pathologic examination=20
- Symmetrical loss of myelin in the posterior and lateral columns = of the=20 spinal cord=20
- Patchy demyelination in the cerebral white matter
MRI of the spinal cord=20
- Often shows white-matter lesions, which resolve with treatment =
Serum cobalamin level: low=20
Anemia

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Best Therapy

Central Pontine Myelinolysis

No specific therapy

Vitamin B₁₂ Deficiency

Cobalamin=20
- Dose: 1,000 =B5g/wk parenterally for 6 wk, then monthly; or = 2,000 =B5g/day=20 p.o.

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Best References

Healton EB, et al: Medicine (Baltimore) 70:229, 1991

Lindenbaum J, et al: N Engl J Med 318:1720, 1988

Pirzada NA, et al: Mayo Clin Proc 76:559, 2001

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Virus-Induced Demyelination

J. William Lindsey, M.D.
Jerry S. Wolinsky, M.D.
University = of=20 Texas Health Science Center at Houston

Defi= nition/Key=20 Clinical Features
Diff= erential=20 Diagnosis
Best= =20 Tests
Best= =20 Therapy
Best= =20 References

Definition/Key=20 Clinical Features

Progressive Multifocal Encephalopathy =

Lethal disease caused by JC = virus=20 infection of oligodendrocytes in immunocompromised patients
Occurs in 4% of patients = with AIDS=20
Usually presents with = relentlessly=20 progressive focal neurologic deficits, such as hemiparesis or visual = field=20 deficits, or with alterations in mental status=20
Survival 3=965 mo after = diagnosis in=20 AIDS patients

Subacute=20 Sclerosing Panencephalitis

Rare late complication of = measles=20
Initial infection usually = occurs in=20 patients < 2 yr
Mean onset 7 yr after initial infection=20
Progressive cognitive deterioration usually appears first, = followed by=20 motor dysfunction and myoclonus=20
Progressive course with occasional temporary remissions

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Differential=20 Diagnosis

Progressive multifocal leukoencephalopathy=20
Subacute sclerosing panencephalitis=20
Neurosyphilis=20
Acute disseminated encephalomyelitis

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Best=20 Tests

Multifocal Encephalopathy =

Brain MRI=20
- Shows one or more white-matter lesions, hyperintense on=20 T₂-weighted images, and hypointense on = T₁-weighted=20 images=20
- No mass effect=20
- Contrast enhancement is rare
Brain biopsy can confirm diagnosis=20
PCR amplification of JC virus from the CSF can confirm diagnosis = without=20 biopsy

Subacute = Sclerosing=20 Panencephalitis

EEG: shows distinctive abnormalities associated with myoclonus=20
Pathologic examination=20
- Shows active viral infection in the brain=20
- Measles virus protein and RNA detectable in both = oligodendrocytes and=20 neurons=20
- Vigorous inflammatory response

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Best Therapy

Progressive Multifocal Encephalopathy

No effective therapy; correction of immunosuppression if possible =

Subacute Sclerosing Panencephalitis

No effective therapy

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Best References

Antinori A, et al: Neurology 48:687, 1997

Honarmand S, et al: Neurology 63:1489, 2004

Sener RN: AJNR Am J Neuroradiol 25:892, 2004

J. William Lindsey, M.D., has received speaking honoraria from = Teva=20 Pharmaceuticals and Serono. Jerry S. Wolinsky, M.D., has served as a = consultant=20 or speaker for Teva Pharmaceuticals, Serono, and Schering-Plough Corp. =

October 2005

=A9 2008 BC Decker Inc. All rights reserved. =