Second edition

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methotrexate, bevacizumab, cyclophosphamide,
L-asparaginase, cisplatin, cytarabine, interferon-alpha, and
immunoglobulins. Although the mechanism of toxicity is
not clear, it probably involves damage to the vascular
endothelium.
Differential diagnosis
The differential with hypertensive encephalopathy rests on
the presence or absence of severe hypertension: although
patients with the reversible posterior leukoencephalopathy
syndrome may have an elevated pressure, for example a
diastolic pressure of up to 105 mmHg, pressures simply do
not rise to the levels seen in hypertensive encephalopathy.
Bilateral occipital infarction, as seen in the ‘top of the
basilar’ syndrome, is distinguished by the involvement of
the occipital cortex, which is in contrast to the sparing of
the gray matter seen in reversible posterior leukoencephalopathy
syndrome.
Treatment
Potentially offending medications should be discontinued.
Seizure may be treated with lorazepam and fosphenytoin,
as described in Section 7.3. The general treatment of delirium
is discussed in Section 5.3.
10.14 MELAS
MELAS (an acronym derived from mitochondrial
encephalomyopathy, lactic acidosis, and stroke-like
episodes) is a rare inherited disorder characterized by varying
combinations of encephalopathy, stroke-like episodes,
migrainous headaches, seizures, and deafness; as with all
mitochondrial disorders, it displays a maternal pattern of
inheritance. Although almost all cases present before the
age of 40 years, with most occurring before the age of 20
years, later onsets have been reported.
Clinical features
As noted, the clinical presentation is quite varied. Some
may present with stroke-like episodes, with hemiparesis,
hemianopia, cortical blindness or aphasia (Iizuka et al.
2003). Delirium may accompany these episodes and may
persist, only to resolve into a dementia, which, in turn, may
be gradually progressive (Sharfstein et al. 1999). In some
cases, psychosis has been noted (Apostolova et al. 2005).
Seizures may occur, and may be simple partial (Canafoglia
et al. 2001), complex partial (including complex partial
status epilepticus [Leff et al. 1998]) or grand mal in type.
Migrainous headaches may precede, accompany, or follow
any of these symptomatologies.
10.14 MELAS 445
Hearing loss is common, and there may be an associated
clinically apparent myopathy. Diabetes mellitus and
either hypo- or hyperthyroidism may occur.
Diffusion-weighted MR scanning during stroke-like
episodes will reveal areas of increased signal intensity; over
time, these same areas will demonstrate increased signal
intensity on FLAIR imaging. Importantly, these areas generally
do not fall within the area of distribution of any
major vessels and are most commonly seen in the occipital
and parietal lobes.
The electroencephalogram (EEG) may reveal periodic
lateralized epileptiform discharges (PLEDs) in patients with
seizures.
Lactic acidosis is found in both the serum and CSF, and
the CSF total protein is also elevated.
Muscle biopsy reveals ragged red fibers, and genetic testing
for mutations in mitochondrial DNA may reveal characteristic
mutations.
Course
Although the overall course is characterized by progression,
the rate of progression, and the sequence with which
various symptomatologies occur, is quite varied.
Etiology
Mitochondrial dysfunction occurs secondary to mutations
in the gene for mitochondrial tRNA, with proliferation of
abnormal mitochondria in vascular endothelial and
smooth muscle cells. Infarcts, which, as noted earlier, do
not conform to vascular territories, are found to affect
both gray and white matter, primarily in the parietal and
occipital lobes.
Differential diagnosis
MELAS should be suspected in any young person with
recurrent stroke, especially when accompanied by
migrainous headache or hearing loss. CADASIL is high on
the differential and is suggested by the MRI finding of
white matter changes in the anterior portion of the temporal
lobes.
Treatment
Symptomatic treatment of delirium and dementia is
described in Sections 5.3 and 5.1 respectively. Seizures may
be treated with anti-epileptic drugs; however, valproic acid
should be avoided as it may aggravate seizures (Lin et al.
2007). L-arginine, given during stroke-like episodes, may
be followed by improvement (Koga et al. 2005).