A RARE CASE OF PERIPHERAL NEUROPATHY

By:

Dr Jami Swathi

Prof Dr Gowrishankar’s unit

• A 41 yr old male patient came with complaints of:

Numbness of both lower limbs – since 1& half yrs

urinary retention - 6months

• H/ O presenting complaint:

Pt was apparently normal 1 & half yrs ago when he

noticed numbness and decreased appreciation of

sensations of both the lower limbs,

insidious onset, symmetrical, slowly progressive,

was present in the soles of both the feet to

begin with & gradually ascended up to above

the knee level

• h/o slipping of chappals without knowledge +• No h/o buckling of knees• No h/o- difficulty in getting up from squatting position• - weakness or sensory symptoms in upper limbs• - involuntary movements• - trauma• - seizures/ LOC• he also gives history of increased frequency of micturition

with the need to strain to micturate,

decreased appreciation of bladder filling,

a feeling of incomplete evacuation of

bladder

• He also noticed decreased sweating of both the lower limbs

• h/o erectile dysfunction +• h/o vomiting +, repeated episodes between 2-6 am in the

morning, postprandial fullness+• h/o loose stools+• No h/s/o postural hypotension• No h/s/o any cranial nerve involvement• No h/o- weight loss• - cough with expectoration/ hemoptysis• -skin rash, photosensitivity, oral ulcers• No h/o chest pain, palpitations

• past history:

no h/o HTN, DM, TB, BA

• personal history:

non alcoholic/ non smoker

• Family history:

father died of a neurological illness at the age of 45yrs ( had similar complaints)

• O/E:

Conscious

oriented

afebrile

No pallor, icterus, cyanosis, clubbing,

lymphadenopathy, edema

Vitals:

BP: 120/80 mm Hg

PR: 80/ min, regular

Systemic examination:

CVS: WNL

RS: WNL

• CNS:• HIGHER MENTAL FUNCTIONS: normal• CRANIAL NERVES: normal• MOTOR SYSTEM:

Right left

bulk: normal normal

tone: normal normal

power:

UL: 5/5 5/5

LL: mild weakness of EHL Bilaterally

rest – 5/5

PLANTAR flexor flexor

• reflexes: • right left• biceps: ++ ++• triceps: ++ ++• supinator: ++ ++• knee: ++ ++• ankle: + +

• Sensory systems: pain & temp sensations decreased below the level of the knee in a graded manner

• vibration sense impaired upto ASIS level

• Cerebellar system: WNL• No signs of meningeal irritation

Differential diagnosis

• Diabetic neuropathy• Amyloidosis • Hereditary sensory and autonomic neuropathy• HIV related autonomic neuropathy• Paraneoplastic neuropathy• Vasculitis • Vit B12 deficiency

INVESTIGATIONS COMPLETE BLOOD COUNTS

Hb 14 gm/dl

TC 9800 cells/ cu mm

DC P71 L24 M5

ESR 4/12 mm/hr

Platelets 2,46.000 / cu mm

PCV 42.1 %

MCV 84.2 fL

MCHC 33.5 gm/dl

MCH 28.2 PG

liver function tests

Total bilirubin 0.6 mg%

Direct bilirubin 0.2 mg%

SGOT 20 U/L

SGPT 12 U/L

Total protein 7.7 gm%

albumin 4.5 gm%

Alkaline phosphatase 68 U/L

Random bld sugar 110 mg%

renal function tests & serum electrolytes

Urea 28 mg%

Creatinine 0.9 mg%

Na 143 m Eq/L

K 4.4 m Eq/L

HCO3 27 m Eq/ L

• viral markers

HIV negative

HbSAg negative

Anti HCV negative

ANA negative

CRP < 6

RA factor negative

C- ANCA/ P- ANCA negative

Anti SSA / SSB negative

Vit B12 level 406 pg/ml

Chest x ray PA view normal

ECG normal

MRI spine normal

Usg abdomen normal

Urine C/S no growth

Bone marrow biopsy cellular marrow. No abnormal cells seen

Serum protein electrophoresis

normal

Nerve conduction study Motor sensory axonal demyelinating polyradiculo- -neuropathy involving predominantly both the lower limbs

Nerve biopsy Right superficial peroneal nerve with deposits of amyloid

Muscle biopsy Right peroneus brevis- mild muscle atrophy

DIAGNOSIS

AMYLOID POLYRADICULONEUROPATHY- PROBABLY FAMILIAL

APPROACH TO PERIPHERAL NEUROPATHY

• Peripheral neuropathy describes the disorder of peripheral nerves including the:

dorsal & ventral nerve roots, dorsal root ganglia, nerve plexuses ( brachial & lumbosacral) cranial nerves (except I & II), & other sensory, motor & autonomic nerves

Symptoms ??...

Is it a polyneuropathy or mononeuropathy??...

Is it small fiber or large fiber??..

Neuropathies with motor manifestations predominantly

• Motor neuron disease• Multifocal motor neuropathy• GBS• Acute motor axonal neuropathy• Porphyria• Chronic inflammatory polyradiculoneuropathy• CMT• Lead intoxication• Diphtheria

Neuropathies with autonomic system involvement

ACUTE CHRONIC

GBS Diabetes

Porphyria Amyloidosis

Acute panautonomic neuropathy Paraneoplastic

Toxic : vincristine HIV

Hereditary sensory & autonomic neuropathy

AMYLOIDOSIS

Primary systemic amyloidosis

Secondary systemic amyloidosis

Familial ( FAP I, II, III ,IV)

TREATMENT

• Presse Med. 2010 Jan;39(1):17-25. Epub 2009 May 5.• [Liver transplantation for familial amyloid

polyneuropathy].• [Article in French] • Adams D, Slama M, Samuel D.

• Liver transplantation has been proposed as a treatment for FAP because the liver is the main source of variant amyloidogenic TTR. Transplantation makes it possible to eliminate 98% of the variant TTR in the serum, doubles median survival for variant TTRMet30 carriers, and halts the progress of the sensorimotor neuropathy over the long term in 62% of cases. No regression or recurrence has been observed. Poor prognostic factors after liver transplantation are a mutation other than the TTRMet30 variant, severe neuropathy, and late onset. Liver transplantation must be proposed to the symptomatic patients as early as possible

• Liver Transpl. 2010 Apr;16(4):470-3.• Poor outcome after liver transplantation for

transthyretin amyloid neuropathy in a family with an Ala36Pro transthyretin mutation: case report.

• Muller KR, Padbury R, Jeffrey GP, Poplawski NK, Thompson P, Tonkin A, Harley HA.

• South Australian Liver Transplant Unit, Flinders Medical Centre, Bedford Park, South Australia, Australia.

• transthyretin amyloid polyneuropathy secondary to an infrequently reported transthyretin mutation (Ala36Pro) who underwent liver transplantation with poor outcomes.

• Neurology. 2010 Jul 27;75(4):324-7.• Progression of transthyretin amyloid neuropathy after

liver transplantation.• Liepnieks JJ, Zhang LQ, Benson MD.• Indiana University School of Medicine, Department of Pathology and Laboratory Medicine, 635 Barnhill Drive,

Indianapolis, IN 46202-5126, USA

• Survival after liver transplantation for TTR amyloidosis may be associated with progression of neuropathy due to continued deposition of amyloid derived from wild-type TTR.

• Transplantation. 2004 Jan 15;77(1):64-71.• Ten years of international experience with liver

transplantation for familial amyloidotic polyneuropathy: results from the Familial Amyloidotic Polyneuropathy World Transplant Registry.

• Herlenius G, Wilczek HE, Larsson M, Ericzon BG; Familial Amyloidotic Polyneuropathy World Transplant Registry.

•Karolinska Institute, Stockholm, Sweden.

• A total of 54 centers in 16 countries have performed OLT for FAP, and today approximately 60 OLTs are performed annually worldwide. During the last decade, a total of 539 patients have undergone 579 OLTs. Patient survival is excellent (overall 5-year patient survival 77%) and comparable to the survival with OLT performed for other chronic liver disorders, but longer follow-up is needed to compare the outcome after OLT with the natural course of the disease. The main cause of death was cardiac related (39%).

THANK YOU