Neurological manifestations of dm

Neurological manifestations of diabetes melitus..cover almost all variants

1. Neurological manifestations of DM Dr. Ajay Kumar Yadav PGY3,Internal medicine IOM-TUTH , Kathmandu 2075/02/09

2. DIABETIC NEUROPATHY Probably the most common complication of DM Most common neuropathy in the Western world Based upon several large studies-approx 50 pc of pts with diabetes will eventually develop neuropathy S ubstantial morbidity, including recurrent lower extremity infections, ulcerations, and subsequent amputations.

3. Pathogenesis of diabetic neuropathy

4. Classification and staging of diabetic neuropathy

5. Classification of the diabetic neuropathies Hyperglycaemic neuropathy Generalised neuropathies Sensorimotor polyneuropathy Acute painful sensory neuropathy Autonomic neuropathy Focal and multifocal neuropathies Cranial neuropathies Thoracolumbar radiculoneuropathy Focal limb neuropathies {including compression and entrapment neuropathies} Proximal diabetic neuropathy Superimposed chronic inflammatory demyelinating polyneuropathy

6. The most frequently encountered neuropathies include Distal symmetric polyneuropathy ( 50 pc ) Autonomic neuropathy ( 7 pc ) Thoracic and lumbar nerve root disease, causing polyradiculopathies ( 3 pc ) Individual cranial and peripheral nerve involvement causing focal mononeuropathies , especially affecting the oculomotor nerve (cranial nerve III) and the median nerve ( 25 pc ) Asymmetric involvement of multiple peripheral nerves, resulting in a mononeuropathy multiplex @Rochester study

7. Loss of vibratory sensation and altered proprioception reflect large-fiber loss Impairment of pain, light touch, and temperature is secondary to loss of small fibers

8. Types of nerve fibres

9. HYPERGLYCAEMIC NEUROPATHY U ncomfortable dysaesthesiae or pain in the feet and lower legs, which rapidly resolve on establishment of euglycaemia . DIABETIC SENSORY POLYNEUROPATHY C ommonest form of diabetic neuropathy . Distal symmetric polyneuropathy : insidious onset G love and stocking distribution Present with numbness, pain, and paraesthesiae,mainly distally in the lower limbs

10. AUTONOMIC NEUROPATHY

11. Cranial neuropathy Isolated 3 rd nerve palsy with pupillary sparing : MC IV ,VI ,VII cranial nerve can also be affected Entrapment neuropathies Carpal tunnel syndrome : Median nerve Ulnar neuropathy at wrist or elbow Peroneal neuropathy : compression at the fibula

12. DIABETIC TRUNCAL RADICULONEUROPATHY Radicular pain , focal truncal sensory loss, and cutaneous hyperaesthesia and focal weakness of the muscles of the anterior abdominal wall Spontaneous recovery usually occurs within 3 to 6 months . PROXIMAL DIABETIC NEUROPATHY Unilateral or commonly asymmetric bilateral lower limb motor neuropathy ( diabetic amyotrophy ) The onset is most often subacute but it may be insidious. Spontaneous recovery is frequent, although not all patients recover fully

13. Diabetic radiculoplexus neuropathy Aka Diabetic amyotrophy or Burns garland syndrome Severe pain in low back ,hip , and thigh in one leg Atrophy and weakness of proximal and distal muscles in the affected leg apparent within few days or weeks : my progress for 18 months or more Often accompanied or heralded by severe wt loss Slow recovery : residual weakness , sensory loss and pain Lumbosacral ( MC ) > Thoracic > Cervical

14. Diabetic neuropathic cachexia   Diffuse diabetic polyradiculopathy superimposed upon severe peripheral neuropathy. A/w unintended severe weight loss and depression M ost frequently occurs in men with type 2 DM on OHA who are middle-aged or older. Most patients improve spontaneously within 12 to 24 months, although some have residual neurologic deficits. There is no specific therapy, and management is supportive.

15. ACUTE PAINFUL DIABETIC NEUROPATHY Acute or subacute onset C haracterised by burning or aching pain felt mainly in the lower limbs , and very rarely in the hands or over the upper limbs and trunk. Accompanied by widespread cutaneous contact hyperaesthesia Treatment is by strict glycaemic control Recovery usually occurs over a period of 6–9 months

16. Acute painful diabetic neuropathies Treatment-induced diabetic neuropathy ( TIDN ) Diabetic neuropathy that occurs in the setting of unintended severe weight loss: Diabetic neuropathic cachexia Diabetic neuropathy that is seen with intentional weight loss ( diabetic anorexia )

17. Treatment-induced neuropathy of diabetes   (TIND) Aka insulin neuritis S mall fiber neuropathy that occurs in patients with chronic hyperglycemia who experience rapid improvement in glycemic control The main clinical manifestations are severe, treatment-resistant pain and autonomic dysfunction, along with worsening of retinopathy and nephropathy The investigators defined the condition by the acute onset of neuropathic pain or autonomic dysfunction within eight weeks of a large improvement in glycemic control ( ie , a decrease in HbA1C of ≥2 percentage points over three months).

18. Treatment of diabetic neuropathy Strict glycemic control : NCV usually improves but symptom of diabetic neuropathy will not necessarily improve Aggressive control : TIND Treat HTN and dyslipidemia Avoid neurotoxins : alcohol and smoking Suplement vitamin def. Foot care

19. Chronic painful neuropathy : Duloxetine , Amitryptyline , Gabapentin , Pregabalin , Valproate or opoid USFDA approved : Duloxetine and pregabalin No direct comparisons available Switch to other agents if no response or S/E develops

20. Treatment of diabetic autonomic neuropathy Postural hypotension High salt intake Drugs : Fludrocortisone , midodrine , clonidine , octreotide , yohimbine : limited success Gastroparesis Dopamine antgonists ( metoclopropamide , Domperidone ) Erythromycin : motilin receptor antagonist : IV > oral Impotence Intracavernosal injection of PGE1 Sildenafil

21. Diabetic foot

22. Neurological manifestations of hypoglycemia Unlike most other body tissues, the brain requires a continuous supply of glucose . V ery limited endogenous glycogen stores, and does not produce glucose intrinsically . Although it accounts for 2% of body weight , the brain utilizes 25% of the body’s glucose due to its high metabolic rate The brain areas most vulnerable to hypoglycemia are (in order) the subiculum , small and medium sized caudate neurons, area CA1 of the hippocampus, the dentate gyrus and superficial cortical layers, specifically layers 2 and 3

23. Fig. 3. Key Aspects of Hypoglycemia induced Neuronal Cell Death. From Suh : Glia55:1280– 1286 (2007)

24. Recurrent exposure to hypoglycemia, particularly in insulin treated type 1 diabetes, but to a lesser extent in type 2 diabetes can chronically impair the counter-regulatory response to hypoglycemia . Two recognized syndromes H ypoglycemia associated autonomic failure(HAAF) I mpaired awareness of hypoglycemia (IAH).

25. Headache

26. Cognitive disturbances and dementia Longitudinal cohort of 16,667 patients showed a greater risk of dementia among those with hypoglycemic episodes, with an attributable risk of dementia of 2.39% per year

27. Hypoglycemic hemiplegia Incidence : 2% On average the weakness resolved over a period of 1 hr to 3 days once normoglycaemia was maintained. Hypoglycemia must be excluded in a patient presenting with symptoms consistent with TIA or stroke. Current guidelines for the treatment of stroke patients with IV tPA exclude those with a glucose level below 50 mg/ dL if their symptoms are likely attributable to the hypoglycemia

28. Unlike ischemic stroke, hypoglycemic changes on MRI are often bilateral, affect the cortex, hippocampus and basal ganglia , and do not necessarily correspond to a vascular territory Hypoglycemic brain death preferentially affects neurons, whereas ischemia tends to affect glial and endothelial cells as well. Hypoglycemia generally spares axons while damage from ischemia affects all parts of the neuron.

29. Seizure The majority of the seizures were GTCS, most recurred Hypoglycemic coma Most feared, and devastating effects MR images of those in persistent vegetative state from hypoglycemia revealed lesions in the bilateral basal ganglia, cerebral cortex, substantia nigra, and hippocampus Two markers of neuronal injury, NSE and S-100 may predict death or otherwise poor outcome in profound hypoglycemic coma

30. Neurological complications of DKA Ischemic stroke Venous sinus thrombosis CNS infections Cerebral edema Rare but fatal complication Occurs in children who seem to be metabolically returning to normal generally 3-12 hrs after initiation of therapy Incidence : 0.7-1% in chidren 31% of deaths due to DKA 20% of all diabetic death s

31. Hyperglycemic hyperosmotic state The prototypical patient with HHS is an elderly individual with type 2 DM, with a several-week history of polyuria , weight loss, and diminished oral intake that culminates in mental confusion,lethargy , or coma. Relative insulin deficiency and inadequate fluid intake are the underlying causes of HHS

32. CEREBROVASCULAR DISAESE In a study in Sweden , the highest rise was 6-fold in diabetic males but 13-fold in diabetic females. G reatest rise in the 5th and 6th decades Most ischaemic strokes are the result of lacunar infarcts. The main source of thromboembolic strokes in diabetic patients is the internal carotid artery.

33. The frequency of TIA is also increased Hypertension is the main risk factor for strokes in diabetic patients. The prevalence of cerebral haemorrhage and subarachnoid haemorrhage has been reported to be the same or less in diabetic than in nondiabetic patients

34. Some genetic disorders associated with DM MITOCHONDRIAL DISORDERS MODY Maternally inherited diabetes combined with sensorineural deafness (MIDD ) Usually present between 30 and 40 years of age Impaired insulin secretion rather than insulin resistance MELAS Kearns-Sayre syndrome Ragged red fibres

35. FRIEDREICH’S ATAXIA A utosomal recessive spinocerebellar degeneration GAA repeat expansion on chromosome 9q G ene product frataxin : mitochondrial protein : deficiency leads to abnormal energy metabolism . Between 10% and 20% of patients with Friedreich’s ataxia develop diabetes. This always begins after the onset of the neurological symptoms and is insulin dependent. Ketoacidosis may occur

36. WOLFRAM SYNDROME AR inheritance Form of insulin dependent diabetes (type 1) associated with diabetes insipidus , optic atrophy causing blindness and deafness (hence DIDMOAD syndrome) Neurological manifestations include late onset cerebellar ataxia, psychiatric disturbances, anosmia , apnoeic episodes, and startle myoclonus .

37. Congenital malformations of the nervous system 3-8% of all births to diabetic women, representing 2–4-fold increase over non-diabetic mothers. The malformations included anencephaly, microcephaly , hydrocephalus, encephalocele , cerebral diplegia , Dandy-Walker syndrome, Arnold- Chiari malformation, spina bifida, and sacral agenesis . Anencephaly and spina bifida were the commonest, occurring in 0.57% (a 3-fold increase) and 0.56% (a 2-fold increase) respectively . The caudal regression syndrome ( sacral agenesis , phocomelic diabetic embryopathy ), although rare, is particularly associated with maternal diabetes, occurring in 0.2%-0.5% of pregnancies , representing a 200-fold increase over the rate in the general population