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Presenter Dr Prakash Harischandra Moderator- Dr B.P Shelley Prof & HOD Neurology , YMC
Neurological complications occur in almost all patients with severe CKD, potentially affecting all levels of the nervous system, from the CNS through to the PNS. Patients on dialysis tend to be weaker and less active, and to have reduced exercise capacity, when compared with healthy individuals Cognitive impairment, peripheral and autonomic neuropathy are also seen.
Overview
Neurological Complications due to Uremic state or due to its treatment can manifest as symptoms Despite Rx, uremia, like uremic encephalopathy, atherosclerosis,neuropathy and myopathy , dialysis dementia, dysequilibrium syndrome, aggravation of atherosclerosis, cerebrovascular accidents are seen
overview
hypertensive encephalopathy, Wernickes encephalopathy, hemorrhagic stroke, subdural hematoma, osmotic myelinolysis, opportunistic infections, intracranial hypertension and mononeuropathy. Transplantation, Immunosuppresion can give rise to newer infections
CNS Encephalopathy
In patients with renal failure, encephalopathy is common -may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity -It is often associated with headache, visual abnormalities, tremor, asterixis, multifocal myoclonus, chorea and seizures. These signs fluctuate from day to day or sometimes from hour to Hour -Uremic encephalopathy may accompany acute or chronic renal failure, Sx worsen rapidly with deterioration. uremic twitch convulsivesyndrome can be seen Hemodialysis Improves Sx . EEG is non diagnostic but when done serially can give a prognostic value. Neuroimagin not Essential.
Cognitive Dysfunction
Cognitive dysfunction increases in prevalence with CKD severity, potentially affecting up to 80% of patients Cognitive impairment in CKD not only increases the risk of mortality, but also has major implications for informed consent in relation to dialysis initiation and maintenance, and, ultimately, renal transplantation
Dialysis Dementia
Dialysis dementia is a term reserved to describe a syndrome of progressive dementia related to aluminum intoxication and first described several decades ago when aluminum contamination of dialysate fluid and the use of aluminum-containing binders were more prevalent; however, this disorder is now rare.
CNS - Encephalopathy
is a common problem that may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity . Seen both in ARF & CRF , Sx more Pronounced in ARF. EEG findings in uremic encephalopathy are nonspecific but correlate with clinical symptoms and therefore may be of diagnostic value especially if serial studies are performed.
EEG in uremic excessive encephalopathy showing showing generalised slowing with an excess of delta and theta waves and bilateral spikes.
EEG from a patient with uraemic encephalopathy.The recording is predominantly (4-8 Hz) and (4 Hz)wave activity, with no normal (>8-13 Hz) or (>13 Hz)waves
Initial MRI study in a patient with severe hypertension, headache, confusion and visual disturbances reveals typical subcortical edema in the occipital regions with only minimal cortical involvement (arrows) on axial FLAIRsequence (A). One week later, after antihypertensive treatment and clinical improvement, follow-up MRI study reveals complete resolution of the lesions on FLAIR images (B).
Management of Encephalopathy
After other causes of delirium have been ruled out, prompt treatment of uremic encephalopathy with initiation or intensification of renal replacement therapy is indicated. Resolution of symptoms typically occurs within days. Correction of anemia (i.e., hemoglobin <10 g/dL) may also be of benefit. Dietary protein restriction is another adjunctive measure used to delay the development of uremic symptoms,
Stroke
Compared with the general population, stroke event rates and stroke mortality rates are increased six- to 10- fold among patients on dialysis Like the general population, ischemic stroke is more common than hemorrhagic stroke Posterior circulation strokes involving the vertebrobasilar system occur more commonly in patients on dialysis than in the general population
Osmotic myelinolysis
Normally in central basis pontis, but extrapontine regions including the midbrain, thalamus, basal nuclei and cerebellum can be affected as well. Clinically progressive Quadriplegia, Dysarthria, dysphagia, Altered Consciousness, Vertical Gaze palsy Parkinsonism-Basal Ganglia or ataxia - cerebellum affected. MRI, T2-show hyperintense patchy areas of demyelination Usually Fatal, If survives, maximum recovery may require several months. Rx is supportive only. postulated that glial cell edema, which is caused by fluctuating osmotic forces, results in compression of fiber tracts and induces demyelination and eventually cell death .
Can be seen due to Encephalopathy,Drugs or Structural lesions. Asterixis or flapping tremor due to cortical dysfunction which mimic drop attacks. Typical movement disorder in uremic encephalopathy is the uremic twitchconvulsive syndrome that consists of intense asterixis and myoclonic jerks that are accompanied by fasciculations, muscle twitches and seizures Thiamine deficency can casue basal ganglia degenration, movement disorder Chorea. Rx induced Movmnt disorders seen in post Renal transplant Patients . Tacrolimus like drugs causing EPS Sx. RLS is also seen commonly, 20% of patients dialysis does not substantially improve uremic restless legs syndrome, but cool dialysate fluid (36.5C) Rx with levodopa, dopamine agonists, benzodiazepines, gabapentin, clonidine or opioids improvement of RLS symptoms after kidney transplantation has been described The etiology is uncertain, but the association with peripheral neuropathy and CRF is well known.
Opportunistic Infections
Nocardia asteroides, Mycobacterium tuberculosis and Listeria monocytogenes Cryptococcus neoformans, Aspergillus fumigatus, Candida, Pneumocystis carinii, Histoplasma, Mucor and Paracoccidioides species Reactivation of latent viral infection with herpes simplex, cytomegalovirus and JC Polyomavirus are not uncommon severe , rapid progressive dementia, ataxia, visual disturbances and other focal neurologic deficits, generally -vegetative state within 6 months
Neoplasms
Immunosuppresive states predisposition to opportunistic infection De Novo Neoplasia malignant meningioma, primary central nervous system lymphoma Immunosuppressive therapy after renal transplantation , increased risk of lymphoproliferative disease. majority of post-transplantation (PTLD) are of B-cell origin and contain EBV. poor clinical outcome CNS involvement was predominant prior to the use of cyclosporine, currently thoracic, and abdominal are common. Radiotherapy is often applied for locations in the central nervous system. Acyclovir, surgical excision, several combinations of chemotherapeutic agents monoclonal antilymphoma immunotherapy With the increased incidence of urogenital, gastrointestinal, hematologic and endocrine neoplasia expect a higher risk of brain metastasis
Intracranial hypotension
Orthostatic headache, occasionally associated with neck stiffness, nausea, visual disturbances, dizziness, hearing loss or 6th Nerve palsy S/o Hypotension due to reduced CSF . Subdural haematoma could mimic this . Imagin required. CSF pressured to be Measured. Can be due to CSF leak , Dehydration, Uremia
Intracranial Hypertension
Could be primary or sec due to Steroids or Neiplasms Raised ICH -headache, transient visual obscurations, & diplopia due to unilateral or bilateral sixth nerve palsy dizziness, nausea, vomiting, tinnitus. papilledema and progressive optic atrophy with accompanying constriction of the visual field, loss of colour vision and eventually blindness Rx Goal reduce ICH Acetozolamide, furosemide, Steroids.Shunting can be done.
Neuropathy
Neuropathy Peripheral neuropathy Carpal tunnel syndrome Autonomic neuropathy Pruritis
Neuropathy in CRF
Peripheral neuropathy
About 50 per cent of patients starting treatment had clinical evidence of a peripheral neuropathy in early days of dialysis Because of earlier initiation of dialysis these days, neuropathy is usually asymptomatic Nerve conduction abnormalities have been reported in up to 60% of patients receiving dialysis Abnormalities in motor nerve conduction velocity parallel the decline in GFR Uremic neuropathy is a distal, symmetric, mixed sensorimotor polyneuropathy.Loss of ankle vibration sensation and the ankle jerk are often the first manifestations, progressing to a burning sensation in the feet, followed by motor deficit, such as weakness of ankle dorsiflexion
Wasting of intrinsic hand muscles, with prominentbilateral atrophy of thenar muscles, in a patient withsevere neuropathy resulting from chronic kidneydisease
Thiamine Defcient Clinical symptoms and nerve conduction parameters improve rapidly following renal transplantation, often within days of surgery Rapidity of these changes suggests that toxinmediated blockade of neural transmission has an important role in the neurological dysfunction associated with CKD.
Systemic diseases that contribute to ESRD and also affect nerve function Diabetes mellitus Amyloidosis SLE Transplantation Provides a treatment option Recovery seen in 3-6 months .
CTS in CRF
Diagnosis of CTS can be confirmed by measuring a delay in median nerve conduction across the wrist, and also by ultrasound of the wrist demonstrating bone cysts and distortion of the flexor tendons Haemodialysis with a high flux polyacrylonitrile, or haemodiafiltration, have been reported to reduce the deposition of 2microglobulin
Autonomic neuropathy
Autonomic dysfunction is a common and potentially lifethreatening complication of CKD, and can occur in the absence of length-dependent uremic neuropathy. More common in diabetics and elderly patients Cardiovascular autonomic dysfunction in CKD is associated with an increased risk of cardiac arrhythmia and sudden cardiac death Impotence remains the most common symptom of autonomic dysfunction in CKD Other common clinical features include bladder and bowel dysfunction, impaired sweating, and orthostatic intolerance Intradialytic hypotension, Renal transplantation leads to considerable improvement in autonomic function Sildenafil , midodrine can be used to alleviate Sx.
Uremic Myopathy
Leads to proximal muscle weakness and wasting, predominantly in the muscles of the lower limbs Uremic myopathy typically develops with glomerular filtration rates of <25 ml/min, been associated with fatigability and reduced exercise capacity EMG and creatine kinase levels are generally normal, and the diagnosis is, therefore, made largely on clinical grounds. Muscle biopsy tends to demonstrate nonspecific features, including type II fiber atrophy with internalized nuclei and fiber
myopathy
Possible etiologies include :Hyperparathyroidism, Metabolic bone disease with vitamin D deficiency Impaired potassium regulation Accumulation of uremic toxins Carnitine deficiency, which can lead to mitochondrial dysfunction Malnutrition
Presentation in acute delirius/ confusional state is common in CKD patients and can have wide array of differential diagnosis. Cognitive impairment is common in patients on dialysis, typically manifesting as a vascular-type dementia with prominent deficits in executive function Renal transplantation improves cognitive function, peripheral neuropathy and autonomic neuropathy Stroke is a common factor adding to morbidity and mortality in these patients. Management strategies unclear Uremic toxin mediated disturbances in resting axonal membrane potential leads to length-dependent neuropathy in CKD Polyneuropathy, Mononeuropathy, Autonomic neuropathy
Summary
Conclusion
Neurological complications whether due to the uremic state or its treatment, contribute largely to the morbidity and mortality in patients with renal failure. Despite continuous therapeutic progress, most neurological complications of uremia fail to fully respond to dialysis and many are elicited or aggravated by dialysis or renal transplantation.
Refrences
Neurologic complications in chronic renal failure: a retrospective study Clin Pediatr (Phila).1990 Sep;29(9):510-4. Uysal S, Renda Y, Saatci U,Yalaz K Neurological Complications of Chronic Kidney Disease Arun V. Krishnan, PhD, FRACP; Matthew C. Kiernan, PhD, FRACP- Medscape Neurological complications in renal failure: a review R. Brounsa,b, P.P. De Deyna,b, Clinical Neurology and Neurosurgery 107 (2004) 116