Charcot–Marie–Tooth disease: clinical presentation (2)

The disease onset usually occurs in the first two decades of life and subsequently shows a slow progression over decades.

Symptoms and signs indicative of CMT include: pes cavus (or pes planus, often later progressing to cavus deformity); hammer toes; difficulty in running; twisting of the ankle and tripping; difficulty in walking; foot drop; steppage gait; wasting, weakness, and sensory loss of distal segments of lower and then upper limbs; difficulties in hand manipulation; and reduced or absent deep-tendon refl exes.

Other common symptoms and signs are hand tremors, muscle cramps (particularly of the foot and leg), cold feet, foot callosities, and acrocyanosis. Positive sensory symptoms such as paraesthesias arerare, but pain is common, particularly in the feet, lower limbs, and lumbar spine. Onset can sometimes occur so early that it causes hypotonia (floppy baby syndrome), delayed motor development, and toe walking, whereas in other cases, the onset can occur late in life.

The presence of other affected family members is often a clue to diagnosis. All mendelian inheritance modes are described for CMT: this disease is more commonly transmitted as an autosomal-dominant trait; X-linked transmission is not uncommon; and autosomal-recessive inheritance is generally uncommon, except in countries that have a high rate of consanguineous marriages.

Diagnosis, natural history, and management of Charcot-Marie-Tooth disease. Pareyson D, Marchesi C. Lancet Neurol. 2009 Jul;8(7):654-67

 

Charcot–Marie–Tooth disease: clinical presentation (1)

CMT is a genetically heterogeneous disorder, also known as hereditary motor and sensory neuropathy (HMSN) and distal hereditary motor neuropathy (dHMN) when only motor nerves are involved. CMT is caused by mutations in genes that encode myelin, Schwann cells, and axons, and that was involved in  the myelin maintenance, cytoskeleton formation, axonal transport, and mitochondrial metabolism. The final common pathway is axonal degenerative process that mainly involves the largest and longest fibres.

The typical CMT phenotype includes:

• Distal predominance of limb-muscle wasting, weakness, and sensory loss, as well as the disto-proximal progression. Motor symptoms start from the feet, which develop high arches, hammer toes, and intrinsic muscle weakness and wasting.
• The leg is gradually affected, then the lower third of the thigh, producing the typical distal atrophy of the lower limbs. The hands are also affected and then the forearms.
• Sensory loss follows the same pathway, affecting feet and hands, commonly with decreased sensation of vibration, touch, and pain; sometimes proprioceptive sensory loss can cause sensory ataxia.
• Deep-tendon reflxes are reduced or absent following the same distal to proximal gradient. Skeletal deformities, which commonly involve the feet, might also include scoliosis.

Diagnosis, natural history, and management of Charcot-Marie-Tooth disease. Pareyson D, Marchesi C. Lancet Neurol. 2009 Jul;8(7):654-67

 

Guidelines for blood pressure management after acute stroke

The present recommendation is to not treat hypertension in most patients with ischaemic stroke, unless blood pressure exceeds 200 mm Hg to 220 mm Hg (systolic) or 120 mm Hg to 140 mm Hg (diastolic).

Alteplase should only be given if the blood pressure is lower than 185 mm Hg (systolic) and 105 mm Hg to 110 mm Hg (diastolic).

Patients with primary intracerebral haemorrhage can be treated with antihypertensive drugs if systolic blood pressure is higher than 180 mm Hg to 200 mm Hg, if diastolic blood pressure exceeds 105 mm Hg, or if mean arterial pressure is higher than 130 mm Hg to 150 mm Hg.

Current guidelines do not support interventions to increase blood pressure in patients with acute ischaemic stroke.

In patients with acute stroke, blood pressure should be reduced gradually with special attention for possible contraindications. The decrease in blood pressure shouldnot exceed 10–20% of the initial level because of the higher set point of the autoregulation of cerebral blood flow in hypertensive patients and to avoid the risk of poor perfusion of aff ected brain area.

Indications to actively lower blood pressure are haematoma growth or rebleeding in primary intracerebral haemorrhage, or coexisting critical conditions, such as hypertensive encephalopathy, aortic dissection, heart failure, acute myocardial infarction, acute renal failure, or preeclampsia and eclampsia.

Blood pressure as a prognostic factor after acute stroke. Tikhonoff V, Zhang H, Richart T, Staessen JA. Lancet Neurol. 2009 Oct;8(10):938-48.

 

The hypertensive response

An acute hypertensive response occurs within 24 h in up to 80% of patients with acute stroke. This response is an increase of blood pressure above normal (ie, 140 mm Hg systolic or 90 mm Hg diastolic) or above pre-existing levels in previously hypertensive patients.

• The primary cause of the hypertensive response is damage or compression of specific regions in the brain that regulate the activity of the autonomic nervous system.
• Pre-existing hypertension, diabetes mellitus, high concentrations of serum creatinine, and the Cushing reflex (a reactive increase in blood pressure in response to raised intracranial pressure) can all exacerbate the rise in blood pressure.
• Headache, urine retention, infection, and stress associated with admission to hospital can lead to an imbalance in the autonomic nervous system, activate the sympathetic adrenomedullary pathway, and raise the concentrations of circulating catecholamines and inflammatory cytokines, all of which can contribute to the hypertensive response.

Blood pressure tends to decline spontaneously without pharmacological intervention in the first few days to weeks after stroke onset. The change in blood pressure after acute stroke is also associated with the severity of the neurological deficits caused by the stroke. A low to normal blood pressure after acute stroke usually indicates extensive brain damage or concurrent coronary artery heart disease.

Blood pressure as a prognostic factor after acute stroke. Tikhonoff V, Zhang H, Richart T, Staessen JA. Lancet Neurol. 2009 Oct;8(10):938-48.