This document discusses various vitamins and their roles in neurological health and disease. It covers macronutrients and micronutrients including B vitamins, vitamins A, D, E, and their functions. Various neurological conditions caused by deficiencies like myelopathy, neuropathy, ataxia and more are described. Investigations and management of different vitamin deficiency states are provided.

1. NUTRITION
AND
NEUROLOGICAL DISEASE
DR. VINOD SINGH JATAV
SR NEUROLOGY
GMC KOTA

2. Divided in two categories
Macronutrients
• Carbohydrate
• Protein
• Fats
Micronutrients
• Water soluble vitamin- Vit B and C
• Fat soluble- Vit. ADEK
• Minerals- Ca, K ,Na, Iron, Zinc, Cu, Se
IEM
(Inborn error of metabolism)

3. VITAMIN B12
 Methylcobalamin most active
 Absorption -ileum
 Essential for production and maintenance of RBCs and
myelination, neurotransmitter, DNA, and RNA production
RDA:-
 2.4μg for men and non-pregnant women
 2.6μg for pregnant women
 2.8μg for lactating women
 1.5–2μg for children up to 18 years

4. Vitamins and enzymes involved in
Homocysteine metabolism

6. Neurologic manifestations
 Myelopathy ± neuropathy (SACD) optic neuropathy,
autonomic dysfunction, cerebellar ataxia,
 Decreased memory, personality change, psychosis,
emotional lability and rarely, delirium, seizure or coma
 Increased risk of stroke
Hematologic manifestations
 Macrocytosis, immature nuclei, and hypersegmented
granulocytes, pancytopenia

7. Neuroimaging
Spinal cord MRI in vitamin B12 myelopathy. Sagittal
(A) and axial (B) T2-weighted images showing
increased signal in the paramedian aspect of the
dorsal cervical cord (arrows).
INVERTED V /RABBIT EAR SIGN
Predominat involve lower cervical
and upper thoracic
IMAGING DIFFERENTIAL-HIV, Cu def., Friderisch ataxia, vitamin E def, multiple
sclerosis ( not symmetrical and less than 2 vertebrae, Neurosyphillis, sarcoidosis

8. Neuroimaging
FLAIR and T2-weighted images might demonstrate extensive areas of a
high-intensity signal in the periventricular white matter

9. Investigation
Serum Vitamin B12
 Above 350 pg/ml:- normal
 200-350 pg/ml :- borderline
add. Testing- increased MMA and Homocysteine
 <200 pg/ml:- deficient
CBC and blood smear- Anemia, macrocytes, mild leuckopenia,
thrombocytopenia, low reticulocyte count, hypersegmented
neutrophil
NCV-Sensori-motor polyneuropathy, demyelination and axonal
degeneration. ( 76% axonal and 24% demyelinating)
Anti IF antibody (high specific) or anti parietal cell antibody (High
sensitive), serum gastrin level- if suspicion of PA

11. ELEVATED METHYLMALONIC ACID
 Cobalamin deficiency
 Renal insufficiency
 Inherited metabolic disorders
 Hypovolemia
ELEVATED HOMOCYSTEINE
 Cobalamin deficiency
 Folate deficiency
 Pyridoxine deficiency
 Renal insufficiency
 Hypothyroidism
 Psoriasis
 Inherited metabolic disorders
 Hypovolemia

12. Treatment
Parenteral ( methylcobalaim/cyanocobalamin or
hydroxocobalamin):-
 1000 mcg daily for 1 week f/b 1000 mcg once a week for a
month f/b 1000 mcg once a month (cyanocobalamine) or every
2 to 3 month (hydroxycobalamin)
or
 1000 mcg/week until deficiency corrected then per month
(cyanocobalmin), every other month (hydroxycobalamin)
Life long- irreversible condition (gastric bypass surgery, PA)
Oral:- 1000-2000 mcg/d (high dose in PA)

13. Monitoring
Haematological response:
 Increase Hb:- 1-2 week
 Disappear hypersegmented neutrophils :- within 2 week
 Resolve leukopenia and thrombocytopenia:- 4-8 week
 Homocysteine and MMA- two week
Neurological response:
 Symptomatic improvement started within 1-2 week,
maximum upto 6 month and may occur upto 1 year.

14. FOLATE (VITAMIN B9)
 RDA-400 μg/day.
 Central role in the biosynthesis of methionine, SAM
and THF
 Absorption - jejunum > ileum.
 neurological deficits same as B12 deficiency
 Increased frequency of NTDs in babies

16. Laboratory Studies
 Serum folate level:-
Above 4 ng/ml:- normal
From 2 to 4 ng/ml:- borderline
Below 2 ng/ml:- low
 RBC folate level (more reliable) < 150ng/ml s/o folate
deficiency
Management
• 0.4 mg for prophylaxis against neural tube defects
• Deficiency acute-1-5mg/d, maintenance 1mg/d

17. THIAMINE (VITAMIN B1)
 Absorbed in jejunum and ileum
 thiamine diphosphate ( metabolically active form)
 role in energy production (ATP synthesis), myelin sheath
maintenance, and neurotransmitter production.
 RDA- 1.2mg/d
 Deficiency- chronic alcoholism, severe malnutrition,
hyperemesis gravidarum, prolonged parenteral nutrition,
malignancies, immunodeficiency syndromes, liver disease,
hyperthyroidism, and severe anorexia nervosa, Diuretic use

18. Clinical Significance
beriberi, Wernicke encephalopathy and Korsakoff syndrome
 Dry beriberi- sensorimotor distal axonal peripheral
neuropathy and Autonomic neuropathy
 wet beriberi- high cardiac output heart failure state
 Infantile beriberi- 2 and 12 months age
Clinical features -cardiomyopathy, vomiting, diarrhea, failure
to thrive, irritability, nystagmus, ophthalmoplegia, dysphonia,
and respiratory symptoms

19. Wernicke encephalopathy
 classic triad- ocular abnormalities, gait ataxia, and mental
status changes (inability to concentrate, apathy, delirium
and frank psychosis)
 Ocular abnormalities -nystagmus, ophthalmoparesis
 Gait and trunk ataxia (cerebellar and vestibular
dysfunction, sensory neuropathy)
 Involvement of hypothalamic and brainstem autonomic
pathways, seizures, myoclonus, or hearing loss

20. Korsakoff syndrome
 amnestic-confabulatory syndrome
 severe anterograde and retrograde amnesia
 involvement of the anterior and medial thalamic
nuclei
 Alertness, attention, social behavior, and other
aspects of cognitive functioning are generally
preserved
 sensorimotor neuropathy (large fiber
predominant) rapid progressive

21.  While Alcoholic neuropathy-slowly progressive,
painful, predominantly sensory neuropathy, with
preferential involvement of small fiber function
Investigations-
 erythrocyte transketolase activation assay and
measurement of erythrocyte thiamine
diphosphate

22. Neuroimaging
FLAIR axial images A, symmetric high-signal-intensity in hypoglossal (arrows). B, The medial
vestibular nuclei). C, the facial nuclei (arrows) and abducens nuclei (arrowheads). D, The
tectum of the midbrain and the periaqueductal gray matter (arrow). E, The mamillary bodies
(arrows). F, medial thalami and periventricular region of the third ventricle.

23. Neuroimaging
47-year-old woman with a history of alcohol abuse presented with ataxia,
changes in consciousness, and ocular abnormalities. A, FLAIR axial image (No
signal-intensity alteration are seen at the mamillary body level (arrows). B, T1-
weighted contrast axial image Contrast enhancement is seen in the mamillary
bodies (arrows).

24. Management
 parenteral thiamine before administration of
glucose
 200 mg IV/orally tds until symptoms improve
 Wernicke encephalopathy- 500mg tds for 2 to
3 days then 250 mg thiamine given IV or IM
daily for 3 to 5 day
 Oral maintenance with 50 mg-100 mg

25. NIACIN (VITAMIN B3)
 Deficiency- dependent on corn as primary carbohydrate source,
 Corn lacks niacin and tryptophan, other-carcinoid syndrome,
vitamin B6 deficiency, Hartnup syndrome, INH, pyrazinamide,
phenytoin, phenobarbital
 Symptoms- 3D (dermatitis, diarrhea, dementia)
Neurologic symptoms-
 irritability, anxiety, depression, and lack of concentration.
 peripheral neuropathy
 Severe deficiency- spasticity, ataxia, and startle myoclonus
 Unexplained progressive encephalopathy in alcoholics

26.  DX- serum and urine niacin
and
fluorometric assay- urinary metabolites (2-pyridone/N-
methylnicotinamide ratio<2)
Management
 Nicotinic acid- 300mg-500mg in divided dose

27. VITAMIN B6 (PYRIDOXINE)
 pyridoxal-5’-phosphate (PLP), the biologically active coenzyme
 RDA- 1-1.7mg/d(adult)
 Function- synthesis of neurotransmitter (dopamine, serotonin,
GABA), myelin
 Infantile sz.- MC in breastfeeding by malnourished mothers
 Normal birth H/O, Hyperirritability ,exaggerated auditory
startle.
 Recurrent convulsions and may have SE.
 Seizures respond poorly to anticonvulsants.
 Peripheral neuropathy

28.  Valproate, carbamazepine, and phenytoin, levodopa
increase the catabolism of pyridoxine
 Other Isoniazid and penicillamine.
 High doses of pyridoxine (1000 mg/day or more) cause
sensory neuronopathy
Investigations-
 Plasma pyridoxal 5-phosphate (PLP).
 Methionine load test is used as a functional indicator of
vitamin B6 status
 Tryptophan load test ( increase urinary xanthurenic acid
in deficiency)

30. Treatment
 Deficiency- 50- 100mg/d
 INH- 30-50mg/d
Pyridoxine dependent Epilepsy ( PDE) in
neonates-
 Treatment- IV pyridoxine- 100mg (max 500mg)
• Oral pyridoxine 15-30mg/kg/d in divided dose
• prenatal- 100mg/d prevention of intrauterine
seizure
 PLP- 30mg/kg/d divided dose

31. VITAMIN A
 Deficiency - diet consists predominantly of rice and wheat
(grains lacking "-carotene), fat malabsorption syndromes
 The earliest sign - reduced ability to see in dim light.(form
rhodopsin)
 White foamy spots on the conjunctiva (Bitot spots)
 Xerosis, or keratinization, of the conjunctiva and cornea

32.  Neurologic manifestations of vitamin A toxicity include
headache, insomnia, irritability
 Pseudotumor cerebri (≥25000 IU/d for month to year)
 Children- drowsiness, delirium, coma, increased ICP,
bulging fontanelle (in infant), psychiatric symp.
Investigations –
 Normal Serum retinol level- 30 mcg/dL to 65 mcg/dL.
(reference range)
 levels over 100 mcg/dL are suggestive of toxicity

33. VITAMIN D
 Vitamin D def.- dietary insufficiency, inadequate sunlight exposure,
immobility, anticonvulsant use, Malabsorption, hypophosphatemia, and
hyperparathyroidism.
 25-hydroxyvitamin D Levels below 30 ng/mL indicate deficiency
 myopathy characterized by proximal weakness(type II muscle fiber
atrophy)
 creatine kinase level is usually normal or only mildly elevated.
 Independent risk factor for MS, Parkinson disease, stroke cognitive
decline

34.  Investigations- 25-hydroxyvitamin D levels, hypocalcemia,
hypophosphatemia,
 raised parathyroid hormone, raised alkaline phosphatase
Treatment-
 To prevent deficiency 400IU/d
 clinical deficiency-50,000 IU oral vitamin D2 or D3 weekly
may be required for 6 to 8 weeks

35. VITAMIN E
 Free-radical scavenger and an antioxidant
 RDA:- 10 mg/d
 Causes of Vitamin E Deficiency

36. Neurological manifestation
 Spinocerebellar syndrome
 Peripheral neuropathy
 Pigmented retinopathy
 Myopathy
 Nystagmus, ptosis, External opthalmoplegia
Abetalipoprotinemia (Bassen-Kornzweig syndrome)-
 AR, MTP gene mutation
 Impaired fat absorption and fat soluble vitamin
 Neurological syndrome similar to vitamin E def,
acanthocytes, retinal pigment changes

37. AVED-
 TTPA gene mutation chr 8q
 AR
 Impaired incorporation of vitamin E into hepatic lipoprotein
Diagnosis-
 Serum vitamin E level= Normal value 0.8 to 1.2 mg/dl
 Alpha-tocopherol (mg)/total lipid (g) ratio more reliable
 Ratio>0.8 mg is normal (total lipid= cholesterol+ TG)

38. Treatment
 Oral replacement of vitamin E
 Dosages- 800 IU/d to 1200 IU/d
 Parenteral replacement may be needed in severe
cases.
Neuroimaging
Cerebellar atrophy as well as hyperintensity in the
posterior columns of the spinal cord on T2-weighted images
NCV:- axonal sensory neuropathy

39. COPPER
 RDA- 900 mcg/d
 Cause of deficiency
Gastric surgery
Excessive zinc consumption
Dietary deficiency
Enteropathies ( IBD, celiac ds.)
 Infancy results in Menkes disease ( X linked recessive,
ATP7A gene mutation)
 Hematologic findings= anemia (micro or macrocytes)
and neutropenia, Ringed sideroblasts

40. Neurological manifestation
 SACD
 sensorimotor polyneuropathy
 Wrist and foot drop can occur
 Optic neuropathy
 Myopathy and cognitive impairment
Investigations
 decrease in serum copper or ceruloplasmin , 24-hour urinary
copper excretion
 False normal copper in deficiency- pregnancy , inflammatory
condition

41. Neuroimaging
• Increased T2 signal involving dorsal column in cervical
cord
• Signal changes may involve lateral column and central
cord
• No contrast enhancement

42. Treatment
Copper supplement:-
 Oral or parenteral :- copper gluconate or chloride
 Regimen:-8 mg/d for 1 week followed by 6 mg/d
for 1 week followed by 4mg/d for 1 week then 2
mg/d
 Intravenous 2mg elemental copper given for 5
days and then periodically.
 zinc induced deficiency: discontinuation of zinc
use

43. Marchiafava- Bignami disease
 Occur in chronic malnourished alcoholic
 Peak age 40-60yr
 Demyelination or necrosis of corpus callosum
(body>genu>splenium) and subcortical white
matter
 Dementia, psychomotor slowing, behavioural
changes, incontinence, dysarthria, seizure,
hemiparesis,
 Treatment- supportive

44. Axial T1 WI showing hypointensity of the genu (white arrow)
and splenium (white arrowhead) of corpus callosum
Axial T2 WI showing hyperintensity of genu (white arrow)
and splenium (white arrowhead) of corpus callosum
Axial T2 WI revealing cortical-subcortical
hyperintensity involving the right frontal lobe (white
arrow

45. restricted diffusion involving the subcortical right
frontal white matter (black arrow) and genu and
splenium (black arrowhead) of corpus callosum
Sagittal flair image displaying central hypointensity
(suggesting cavitation) with surrounding hyperintense rim
(active inflammation) (white arrowheads) involving the
genu, body, and splenium of corpus callosum (sandwich
sign)

46. Lathyrism
 Occur due to consumption of chickling pea or grass
pea (lathyrus sativus)
 Age:- 15-45 yr
 Toxic amino acid - b-N-oxalylamino-L-alanine ( BOAA)
 Degeneration is most prominent in pyramidal tracts
 Irreversible spastic paraparesis (subacute to
chronic) f/b ankle and knee contracture

47.  Sensory and bowel-bladder involvement may occur
Investigation
 Clinical diagnosis
 MRI study are negative
Treatment:-Supportive

48. Calcium
Hypocalcemia-( <8.5mg/dl or ionized calcium<1.0 mmol/l)
 Neuromuscular symptoms- tingling or numbness in
perioral area or finger and toes, tetany, bronchospasm,
dysphagia
 Neurological symptoms-impaired intellectual, irritability,
confusion, seizure, fatigue, movement abnormality
(choreoathetosis, dystonia)
Hypercalcemia- (>10.5mg/dl)
 Neurological manifestation- cognitive dysfunction,
depression lethargy, confusion, coma

49. Trace
element
deficiency
Neurological manifestation
Zn Increase risk of Alzheimer’s disease, Depression, Stroke, Epilepsy,
cognitive impairments, impaired learning and memory
Mg low Mg level is associated with migraine, Alzheimer’s disease,
cerebrovascular disease, hypertension, cardiovascular diseases
Se cognitive impairment, depression, and anxiety, low level found in
Alzheimer’s disease, Parkinson disease
Iron iron deficiency anemia in adults is a risk factor for cerebral venous
thrombosis, ADHD in children
Iodine Abortion, stillbirth, Low IQ, mental retardation, dwarfism, deaf-
mutism, spastic diplegia, psychiatric symp., Goiter, low thyroid
hormone

50. References
 Bradely’s Neurology In Clinical Practise, 7th Edition
 Harrison’s Principle Of Internal Medicine,20th Edition
 Continuum (Minneap Minn) 2017;23(3):822–861.
 B Vitamins in the nervous system: Current knowledge of the
biochemical modes of action and synergies of thiamine, pyridoxine, and
cobalamin Carlos Alberto Calderón‐Ospina, Mauricio Orlando
Nava‐Mesa CNS Neurosci Ther. 2020
 Kathyayini Paidipati Gopalkishna Murthy, "Magnetic Resonance Imaging
in Marchiafava-Bignami Syndrome: A Cornerstone in Diagnosis and
Prognosis", Case Reports in Radiology, vol. 2014,
 Up to date.com
 Bioactive Nutraceuticals and Dietary Supplements in Neurological and
Brain Disease -The Effects of Trace Element Deficiencies on Neurological
Disease and Treatment with Trace Element Support

51. THANK YOU