Systemic & Metabolic Disorders Flashcards
Vitamin deficiencies and neurologic symptoms
Which substance inactivates cyanocobalamin and causes vitamin B12 deficiency myeloneuropathy?
Nitrus oxide (surgical sedation)
Either from nitrus oxide abuse, or therapeutic use in patients with subclinical B12 deficiency
Abetalipoproteinemia (Bassen-Kornzweig disease): cause and clinical/ laboratory findings
autosomal recessive disorder caused by mutations in the microsomal triglyceride transfer protein (MTTP) gene
This leads to a multiple vitamin deficiency, affecting the fat-soluble vitamin A, vitamin D, vitamin E, and vitamin K.
The neurologic manifestations of abetalipoproteinemia result from the inability to absorb and transport vitamin E.
Vitamin A deficiency may also contribute to the retinal degeneration. Neuropathologic changes affect posterior columns and spinocerebellar tracts.
Clinical features
This disorder typically presents in early childhood with steatorrhea, abdominal distension, and failure to thrive.
During childhood or adolescence, progressive ataxia, neuropathy, and vision impairment develop.
Funduscopic examination reveals pigmentary degeneration of the retina (retinitis pigmentosa).
Dysarthria is common. The sensory motor neuropathy manifests with weakness and distal muscle atrophy. Reflexes are diminished or absent, although extensor plantar responses may be present.
There is truncal and limb ataxia. Proprioceptive sensory loss and possibly impaired pain and temperature sensation occur as well.
Characteristic laboratory findings include:
● Triglyceride levels and total cholesterol levels are very low
● Acanthocytes constitute 50 to 90 percent of the circulating red blood cell population. A mild, normocytic anemia is common.
● Sensory nerve conduction studies have shown absent SNAPs or SNAPs of reduced amplitudes. Conduction velocities are usually normal. Motor nerve conduction studies may be normal.
● Vitamin E levels (alpha-tocopherol and gamma-tocopherol) are undetectable or very low.
● Some patients develop elevated transaminases due to hepatic steatosis
● Homozygotes may have an impaired cortisol response to adrenocorticotrophic hormone (ACTH).
Osmotic demyelination syndrome clinical findings
The clinical manifestations of ODS are typically delayed for two to six days after overly rapid elevation of the serum sodium concentration has occurred.
The symptoms, which are often irreversible or only partially reversible, include:
* dysarthria
* dysphagia
* paraparesis or quadriparesis
* behavioral disturbances
* movement disorders
* seizures
* lethargy, confusion, disorientation and coma
Severely affected patients may become “locked in”; they are awake but are unable to move or verbally communicate.
Other common findings include increased muscle tone and facial weakness, as well as snout (απομύζησης), grasp, or rooting reflexes.
the rate of correction of hyponatremia should not exceed 6 to 8 mEq/L in any 24-hour period!!
Osmotic demyelination syndrome imaging
MRI
The earliest change is seen on DWI with restriction in the lower pons.
This is seen within 24 hours of the onset of quadriplegia.
This same region demonstrates eventual high T2 signal and later a low T1 signal. The T1 and T2 changes may take up to two weeks to develop.
This region has a classic trident-shaped appearance.
Occasionally gadolinium enhancement is also demonstrated, just as in the acute phase of multiple sclerosis plaque.
Similar appearances are seen in other parts of the brain: basal ganglia, midbrain, and subcortical white matter
Osmotic demyelinating syndrome management
Patients with suspected ODS (ie, onset of symptoms consistent with ODS in a patient with risk factors, such as overly rapid correction of hyponatremia) should have their serum sodium relowered; efforts to relower the sodium should commence without waiting for imaging confirmation of demyelinating lesions (which may take weeks to appear).
Desmopressin or D5W –> goal: Na less than 16 from the initial Na
Relowering of the serum sodium is less likely to be of benefit later in the patient’s course.
In addition, patients who have developed ODS as a consequence of hyponatremia correction often require intensive supportive therapy.
Clinical sign of hypermagnesemia/ hypomagnesemia
Hypermagnesemia –> Depressed deep tendon reflexes
Hypomagnesemia –> Hyperreflexia
Hypertensive Encephalopathy: definition
Hypertensive encephalopathy refers to the presence of signs and/or symptoms of cerebral edema caused by severe and/or sudden rises in BP.
Hypertensive encephalopathy: clinical findings and diagnosis
insidious onset of headache, nausea, and vomiting, followed by nonlocalizing neurologic symptoms such as restlessness, confusion, and, if the hypertension is not treated, seizures and coma
Hypertensive encephalopathy is a diagnosis of exclusion, confirmed retrospectively when neurologic symptoms improve after the BP is lowered!!
However, cerebral imaging, particularly MRI with T2-weighted images, may reveal edema of the white matter of the parieto-occipital regions, a finding consistent with hypertensive encephalopathy that is termed reversible posterior leukoencephalopathy syndrome
PRES risk factors
https://www.uptodate.com/contents/image?imageKey=NEURO%2F51758&topicKey=NEURO%2F4835&search=hypertensive%20encephalopathy&source=see_link
Posterior reversible encephalopathy syndrome: clinical and imaging features
- The typical clinical syndrome includes headache, confusion, visual symptoms, and seizures
- Typical MRI findings are consistent with vasogenic edema in the subcortical white matter and are predominantly localized to the posterior cerebral hemispheres. The differentiation of vasogenic versus cytotoxic edema with DWI is helpful in distinguishing RPLS from stroke.
What distinguishes PRES from stroke in imaging
Vasogenic edema
the calcarine and paramedian parts of the occipital lobe are usually spared, helping to distinguish RPLS from bilateral posterior cerebral infarctions
Relative sparing of the cortical gray matter in RPLS also distinguishes this from posterior cerebral artery infarction
Endocarditis: when should be suspected
The diagnosis of IE should be suspected in patients with bacteremia due to an organism with known propensity to cause endocarditis
other important clues include fever, relevant cardiac risk factors (prior IE, history of valvular, or congenital heart disease), and other predisposing conditions (intravenous drug use, indwelling intravenous lines, immunosuppression, or a recent dental or surgical procedure).
Endocarditis neurologic complications
● Embolic stroke
● Brain abscess or cerebritis
● Purulent or aseptic meningitis
● Acute encephalopathy
● Meningoencephalitis
● Cerebral hemorrhage (due to stroke or a ruptured mycotic aneurysm)
● Seizures (secondary to abscess or embolic infarction)
Antithrombotic therapy in patients with infective endocarditis without ischemic stroke (patients already taking anticoagulation)
● Anticoagulant or antiplatelet therapy is not indicated to reduce the risk of thromboembolic complications of IE.
● Patients with IE frequently have one or more coexistent conditions that pose a risk of thrombotic complications separate from IE.
In such patients, we weigh the risk of withholding antithrombotic therapy against the risk of antithrombotic therapy (particularly the risk of intracerebral hemorrhage).
If there is a strong indication for antithrombotic therapy in a patient with IE, we continue antithrombotic therapy after reviewing the echocardiogram and excluding contraindications such as an intracerebral hemorrhage or ischemic stroke by imaging
*Patients with strong indications for continuing antithrombotic therapy in the setting of IE include those with mechanical prosthetic valves
*Antiplatelet therapy for IE patients with coronary artery disease should be governed by the applicable recommendations for coronary artery disease, including specific recommendations for patients who have undergone coronary artery stenting. This includes continuing aspirin indefinitely in all patients with coronary stents, in addition to time-limited dual antiplatelet therapy.
*Anticoagulant therapy (rather than antiplatelet therapy) is recommended in IE patients with atrial fibrillation with a CHA2DS2-VASc score of 2 or greater
*Anticoagulation is recommended in IE patients with atrial fibrillation with mitral stenosis regardless of the CHA2DS2-VASc score
● In patients with IE in whom a decision is made to continue anticoagulant therapy (eg, for a mechanical valve), we generally replace direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA) therapy (eg, warfarin) with unfractionated heparin or low molecular weight heparin therapy at the time of presentation while stability and the potential need for an invasive procedure is assessed
Antithrombotic treatment in patients with endocarditis and ischemic stroke
In most patients with IE on anticoagulation who develop an acute ischemic stroke, we suggest discontinuing anticoagulant therapy for at least two weeks due to the risk of hemorrhagic transformation.
In addition, we suggest not starting aspirin or other antiplatelet agents for patients with IE who have an acute ischemic stroke or TIA.
The optimal length of time for discontinuation of anticoagulation is unknown and is based on limited evidence
An exception applies to patients judged to have high risk of cardioembolic stroke (above the general risk of stroke associated with IE; eg, a patient with a mechanical valve with high-risk features) in whom cautious anticoagulation may be continued if the ischemic stroke is small, although this recommendation is controversial.
If there is a compelling need to reinstitute anticoagulant therapy during the first two weeks following the onset of stroke (eg, presence of a mechanical valve, particularly with high-risk features), serial brain imaging with computed tomography or magnetic resonance imaging should be performed to exclude hemorrhagic transformation or intraparenchymal hemorrhage
Thrombolytic therapy is generally contraindicated in patients with IE and stroke
Hypoxic - ischemic encephalopathy prognostic factors
● Absent pupillary or corneal reflexes at three days after cardiac arrest are invariably associated with a poor outcome.
Motor responses at day 3 are not reliable indicators in patients treated with hypothermia.
● Bilaterally absent somatosensory evoked responses at 24 to 72 hours may be useful to identify those with a poor prognosis. While very specific, these signs are not very sensitive for poor neurologic outcome.
● Biomarkers (eg, neuron-specific enolase [NSE]) appear to be promising indicators of poor outcome, but have uncertain predictive value at least for those patients treated with hypothermia. Further research is needed to better define their cutoff values and sensitivity.
● It is helpful to have two indicators of poor outcome before concluding that the patient will be severely disabled.
● Potential confounding factors in the clinical assessment of patients in hypoxic-ischemic coma include acute metabolic derangements (eg, renal failure, liver failure, shock), the administration of sedative or neuromuscular agents, and induced-hypothermia therapy.
Hepatic encephalopathy clinical findings and diagnosis
Hepatic encephalopathy is characterized by cognitive deficits and impaired neuromuscular function
Cognitive findings in patients with hepatic encephalopathy vary from subtle deficits that are not apparent without specialized testing (minimal hepatic encephalopathy) to more overt findings, with impairments in attention, reaction time, and working memory.
Patients with severe hepatic encephalopathy may progress to hepatic coma.
Neuromuscular impairments include bradykinesia, hyperreflexia, rigidity, myoclonus, and asterixis (πτερυγοειδής τρόμος).
Disturbances in the diurnal sleep pattern (insomnia and hypersomnia) are common initial manifestations of hepatic encephalopathy and typically precede other mental status changes or neuromuscular symptoms
Which condition is associated with cerebral aneurysms
Polycystic kidney disease
Which pathogen should be suspected in CNS infection in patients with advanced renal failure
Listeria monocytogens
Systemic condition that causes restless leg syndrome
Renal failure
Percentage of dialysis patients with uremic polyneuropathy
> 50%
Neurologic complications of renal insufficiency
Dialysis disequilibrium syndrome Risk factors and clinical findings
● Risk factors – New patients being initiated on intermittent hemodialysis, particularly if the blood urea nitrogen is markedly elevated (eg, >175 mg/dL or 60 mmol/L).
Other predisposing factors include extremes of age, preexisting neurologic diseases (eg, head trauma, seizure disorder), conditions associated with an increased permeability of the blood-brain barrier (eg, encephalitis), and concomitant presence of other conditions that are associated with cerebral edema (eg, hepatic encephalopathy)
● Pathogenesis – The symptoms of DDS are caused by cerebral edema, but the mechanism for development of cerebral edema is unclear. The prevailing theory is that rapid clearance of urea and other osmoles by hemodialysis results in a rapid fall in the plasma osmolality, which leads to movement of water into the neurons.
● Clinical manifestations – Clinical manifestations of DDS include headache, nausea, blurred vision, and restlessness that can progress to somnolence, confusion, disorientation, or mania.
Mild symptoms are usually self-limited in most patients.
However, severe manifestations can include seizures, stupor, coma, and death
Uremic encephalopathy clinical findings
Early clinical features of uremic encephalopathy include lethargy, irritability, disorientation, hallucinations, and rambling speech.
Coma is unusual but may occur in patients with acute renal failure!
Most uremic patients have mild diffuse weakness and show unsteadiness in their movements.
Tremor, myoclonus, and asterixis are common and tend to vary in parallel with mental status; tetany may be present.
Rarely, focal signs such as hemiparesis or reflex asymmetry may occur. Such focal signs tend to be transient, alternate from side to side, and resolve with hemodialysis
Generalized seizures may occur, particularly when uremia is acute, and myoclonus, psychosis, and coma can also be seen
Neurologic manifestations of hyperthyroidism
Neurologic manifestations of hypothyroidism
Hashimoto encephalopathy: clinical findings, diagnosis and treatment
● Clinical presentation –
The presentation is heterogeneous with a fulminant, subacute, or more chronic course of declining mental status that is frequently accompanied by seizures and myoclonus.
Some patients present with coma and others with isolated psychiatric features.
● Evaluation and diagnosis –
The presence of elevated antithyroid antibody titers (antithyroid peroxidase antibody (TPOAb) and/or antithyroglobulin antibody (TgAb)) and the exclusion of other causes of encephalopathy support the diagnosis of HE.
While the entity of HE is disputed, there appears to be enough evidence to support checking antithyroid antibody levels as a second- or third-tier diagnostic test in patients presenting with unexplained encephalopathy and considering the diagnosis of HE if levels are elevated.
● Management –
In a patient with encephalopathy and elevated antithyroid antibody levels in whom other causes of encephalopathy are rigorously excluded, we suggest an initial trial of glucocorticoid therapy rather than other immunosuppressive therapies
Other immunosuppressive treatments have also been used in patients who cannot take glucocorticoids, who are refractory to glucocorticoids, or who relapse after initial treatment.
(including azathioprine, cyclophosphamide, methotrexate, rituximab, and hydroxychloroquine)
Systemic vasculitides
Neuropsychiatric manifestations os systemic lupus eryhthematosus
