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
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
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
15.
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)
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
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
Naturally occurring form of B12- methyl, hydroxy, adenosylcobalamin and cyanocobalamin is synthetic form,
Absorb by two mechanism IF related and passive diffusion
B12 also require for conversion of methylmalonylcoA to succinyl coA
In deficiencies of either folate or cobalamin, there is failure to convert deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), the precursor of dTTP This is the case because folate is needed as the coenzyme 5,10-methylene-THF polyglutamate for conversion of dUMP to dTMP; the availability of 5,10-methylene-THF is reduced in either cobalamin or folate deficiency
Antiepileptic –phenytoin and carbamazapine
Glossitis, Skin hyperpigmentation
Cyanocobalamin is inferior to other form of b12 because of low tissue retention, and high urinary excretion compare to other
INH, methotrexate
Require for metabolism of carbohydrate, lipid and protein
Also used in hyperlipidemia
2 other rare cause of pyridoxine responsive seizure- mutation in ALDH7A1 lead to deficiency of antiquitin and inactivation of PLP
Other deficiency of PNPO ( pyridoxamine phosphate oxidase) lead to decrease syhesis of PLP
BOAA is excitotoxic at AMPA receptor, increased calcium in cytoplasm
Zn – role in cell division, and apoptosis, immunity
Mg- cofactor in enzyme , blockade of calcium in NMDA receptor
Se- antioxidant, immune function
Fe- Microcytic red blood cells increase the viscosity
Iodine- cretinism
