This is about Uremic Encephalopathy. It describes the symptoms and features of uremic encephalopathy and other related issues.

1. NEUROLOGICAL COMPLICATIONS
OF NEPHROLOGICAL DISORDERS
DR SAUMYA H MITTAL.
CONSULTANT NEUROLOGIST.
SHARDA MEDICAL COLLEGE AND HOSPITAL.

2. • In relation to the nephrological diseases,
neurologic complications occur due to-
– Renal disease.
– Dialysis.
– Renal transplantation.
– Renal carcinoma, chemotherapy and radiotherapy.

3. Conditions Related to Kidney
• UREMIC ENCEPHALOPATHY.
• UREMIC NEUROPATHY.
– Autonomic neuropathy.
– Peripheral neuropathy.
• UREMIC MYOPATHY.
• RESTLESS LEG SYNDROME.
• STROKE.
• OPTIC NEUROPATHY.
• PRES.
• GB SYNDROME.
• CEREBRAL VENOUS
THROMBOSIS.
• MYASTHENIA GRAVIS.
Conditions Related to Dialysis
• COGNITIVE IMPAIRMENT.
• SUBDURAL HEMORRHAGE.
• PARKINSONISM.
• OPTIC NEUROPATHY.
• MUSCLE CRAMPS.
• DIALYSIS DYSEQUILIBRIUM
SYNDROME.
• STROKE.
• OSMOTIC DEMYELINATION
SYNDROME.
• CONVULSIONS.
• SLEEP DISORDERS.
• MONONEUROPATHIES
– CARPAL TUNNEL SYNDROME.
– ULNAR NEUROPATHIES.
• WERNICKE’ ENCEPHALOPATHY.
• OPHTHALMOPLEGIA.
• ATAXIA.

4. • ACUTE REJECTION
ENCEPHALOPATHY.
• HEADACHES.
• COMA.
• SEIZURES.
• HYDROCEPHALUS.
• NEUROPATHY.
• BRAIN TUMORS.
• MALIGNANCIES AND
PARANEOPLASTIC SYNDROME.
• CNS INFECTIONS.
• IMMUNOSUPPRESANTS
RELATED NEUROTOXICITY.
Conditions Related to Hereditary
Disorders
• FABRY DISEASE.
– NEUROPATHY.
– LIMB PAIN.
– DYSAUTONOMIA.
– STROKE.
– VBI.
– WHITE MATTER LESIONS.
• VON HIPPEL LANDAU DISEASE.
– CNS HEMANGIOBLASTOMAS..
– VISUAL COMPLICATIONS.
• POLYCYSTIC KIDNEY DISEASES
– SAH.
– ICH.
– ANEURYSMS.
Conditions Related to
Transplantation

5. UREMIC ENCEPHALOPATHY
• Resembles any other metabolic and toxic disorders of
CNS.
• Etiology-
– Consequences of uremia,
– Dialysis,
– Thiamine deficiency,
– Drug toxicity,
– Transplant rejection.
• Encephalopathy and renal impairment may both relate
independently to the same underlying systemic illness
– Diabetes,
– Connective tissue diseases.

6. • Uremic encephalopathy most commonly
relates to
– a variety of metabolic abnormalities,
– with the accumulation of numerous metabolites,
– imbalance in excitatory and inhibitory
neurotransmitters, and
– hormonal disturbances leading to cerebral
dysfunction.

7. • Metabolite abnormalities:
– 90 compounds considered to be uremic toxins.
– Retention of urea occurs.
– Accumulation of guanidine compounds
(guanidinosuccinic acid, methylguanidine,
guanidine, and creatinine) cause uremic seizures
and cognitive dysfunction.
– Guanidinosuccinic acid accumulation (may inhibit
transketolase, a thiamine-dependent enzyme)
affects the maintenance of myelin.
– Low-level aluminum overload in renal failure
causes gradual deterioration in cerebral function.

8. • Neurotransmitter and Receptor abnormality:
– Activation of N-methyl-d-aspartate (NMDA)
receptors and inhibition of γ-aminobutyric acid-A
(GABA-A) transmission may be involved.
– Abnormalities of the membrane pumps, both
Na+,K+–ATPase and calcium ions, are known.

9. • Hormonal changes in uremic encephalopathy-
elevated serum concentrations of
– parathyroid hormone,
– growth hormone,
– prolactin,
– luteinizing hormone,
– insulin, and
– glucagon are known.

10. • Parathyroid hormone levels increase with the
severity of the encephalopathy.
• Calcium content of the cerebral cortex is greatly
increased in uremia.
• Alterations in brain calcium influence cerebral
function d/t abnormal
– neurotransmitter release,
– the sodium-potassium pump,
– intracellular enzyme activity, and
– intracellular metabolic processes.
• Both clinical and EEG abnormalities, and changes
in cerebral calcium concentration, are improved
by parathyroidectomy.

11. • The clinical features of the encephalopathy
include
– Waxing and waning impairment of external
awareness.
– Ability to concentrate is impaired:
• patients seem preoccupied,
• apathetic,
• poor attention span,
• become increasingly disoriented.
• exhibit emotional lability,
• and sleep inversion.

12. – With progression, patients become more
obtunded
• it may then be necessary to shout or gently shake them
to engage their attention and elicit any responses.
– Delusions, illusions, and hallucinations (typically
visual) develop.
– Patients may develop an acute delirium
• Appear to be agitated and excited.
– Eventually replaced by stupor and a preterminal
coma.

13. • Seizures are common.
• They are usually
– Generalized convulsions,
• In acute renal failure, seizures occur within days of onset
(oligoanuria).
• In chronic renal failure, they occur with advanced disease,
often preterminally;
• May be multiple,
• Are often multifactorial in etiology.
– they may relate to the uremia
– to electrolyte disturbances,
– medications (such as penicillin, aminophylline, or isoniazid),
– associated reversible posterior leukoencephalopathy syndrome
– as part of the dialysis dysequilibrium syndrome.

14. • Their incidence has declined, due to
– More effective treatment of renal failure and
– Better selection of AEDs.
– Focal seizures sometimes occur.
– Non-convulsive status epilepticus may not be
recognized unless an EEG is obtained.
– Spontaneous and stimulus-sensitive myoclonus is
common in uremia as in other metabolic
encephalopathies.

15. • Movement Disorders are seen
– Tremulousness may be conspicuous and usually
occurs before asterixis is found. Tremors could be of 2
types
• Coarse postural tremor is seen in the fingers of the
outstretched hands, and
• Kinetic tremor are also common.
– Asterixis/flapping tremors is a nonspecific sign of
metabolic cerebral dysfunction. Affects-
• Upper limbs.
• Neck and Trunk.
• Eyelids.
• Lips.
• Tongue.
• Lower limbs at hip joints.

16. – Multifocal myoclonus is sometimes so intense that
muscles appear to be fasciculating (uremic
twitching).
– Paratonia (gegenhalten is common.

17. • Disorders of Movement may be seen
– During the early stages of uremia, patients may be
clumsy or have an unsteady gait.
– Extensor muscle tone increases asymmetrically.
– Opisthotonos or decorticate posturing of the limbs
may eventually occur.

18. • Motor deficits may include
– transient or alternating hemiparesis,
– flaccid quadriparesis, or
– distal weakness.

19. • Lab Investigations include-
– RFT.
– CSF analysis.
– EEG.
– Brain Imaging.

20. AED Total Daily Dose* Dialysis ^
Phenytoin Same Same
Phenobarbital Reduce Reduces
Primidone Reduce Same
Valproic acid Same Same
Carbamazepine Same Same
Gabapentin Reduce Increases
Pregabalin Reduce Increases
Topiramate Reduce Increases
Zonisamide Reduce Same
Levetiracetam Same Increases
Tiagabine Same
Lamotrigine Same Same
Felbamate Reduce
Vigabatrin Reduce
Oxcarbazepine Reduce Same
Lacosamide Same Increases
*Some doses may need changes in the later stages.
^ Level of plasma protein, type of dialyzer can make a difference.

21. • Laboratory studies provide evidence of impaired
renal function but are of limited utility in
monitoring the course of the encephalopathy.
• Furthermore, abnormal renal function tests do
not exclude other causes of encephalopathy.
• An underlying structural lesion must be excluded
in uremic patients especially after seizures.

22. THANK YOU