CPC 4 ธนัวาคม พ.ศ. 2551

อายรุแพทย์ รศ.พญ. นิจศรี ชาญณรงค์ผูป่้วยชายไทยคู ่ อาย ุ 45 ปี อาชพีขายน ้าเตา้หู-้ปาทอ่งโก๋ภมูลิ าเนาและทีอ่ยูปั่จจบุนั ต.หว้ยตามอญ อ.ภสูงิห ์ จ.อตุรดถิต์1st admission ประวตัไิดจ้ากผูป่้วย และเวชระเบยีน เชือ่ถอืได ้CC: ขาสองขา้งออ่นแรง 1 เดอืน PTAPI: 5 เดอืน PTA รูส้กึหนา ๆ บวมๆ บรเิวณตัง้แตข่อ้เทา้ถงึปลายนิว้เทา้

ขวา บางครัง้รูส้กึเหมอืนมอีะไรมาแทงฝ่าเทา้เวลาเหยยีบพืน้ ไมม่อีาการแขนขาออ่นแรง ขบัถา่ยปกต ิ ไปรับการรักษาทีค่ลนิกิใกลบ้า้น แพทย์วนิจิฉัยวา่เป็นเกา๊ต ์ใหย้าขบัปัสสาวะ และ allopurinol มารับประทาน อาการไมด่ขี ึน้ ความรูส้กึหนา ๆ และเจ็บทีบ่รเิวณฝ่าเทา้เป็นเทา่ ๆ เดมิ มีคนทักวา่ผวิสคีล ้าขึน้ สงัเกตวา่เป็นมากบรเิวณทีถ่กูแสงแดด3 ½ เดอืน PTA เริม่รูส้กึใสร่องเทา้แลว้เทา้ขวาหลดุงา่ย อาการหนาๆ บวม ๆ ยงัคงอยูเ่ทา่ ๆ เดมิ ปัสสาวะอจุจาระปกตดิี2 ½ เดอืน PTA เริม่มอีาการปลายนิว้เทา้ซา้ยมชีา ฝ่าเทา้ทัง้สองขา้งเหมอืนมอีะไรมาแทงเวลาเหยยีบพืน้ 1 เดอืน PTA เทา้ซา้ยใสร่องเทา้แลว้หลดุ เดนิลากเทา้ไมไ่ด ้ ตอ้งยกเทา้ขึน้สงู ขา้งขวาเป็นมากกวา่ขา้งซา้ย ชามากบรเิวณปลายนิว้เทา้ทัง้สองขา้ง ไมม่แีขนออ่นแรง ปัสสาวะอจุจาระปกตดิ ี

5 mo. Sensory3.5 mo. Motor

2.5 mo. Sensory1 mo. Motor

น ้าหนักลดลง (80 73 กก.) ในชว่ง 5 เดอืน มีคนทักวา่ผวิคล ้าขึน้ ไมป่วดหลัง ไมม่ไีข ้ ขบัถา่ยปกต ิ ไมม่อีบุัตเิหตกุระทบกระเทอืนทีห่ลัง

PH: ความดนัโลหติสงู เคยกนิยาแลว้ความดันปกต ิ แพทยใ์หห้ยดุยา

Hyperuricemia 1-2 yr. ได ้ Allopurinol (300) 1x1

ปฏเิสธใชย้าชดุ ยาหมอ้ ยาลกูกลอน

ปฏเิสธแพย้า

ปฏเิสธดืม่สรุา,สบูบหุรี่

ปฏเิสธอาการผืน่แพแ้สง แผลในปาก ปวดขอ้

FH: ปฏเิสธประวัตโิรคทางระบบประสาทในครอบครัว

Physical Examination:Vital signs: BT 37 º C , PR 100 /min, BP 159/95 mmHg,

RR 20 /minGA: A Thai middle aged male, good consciousnessSkin and appendages: No rash, hyperpigmented skin at

sun-exposure areas (as pictures)

HEENT: Not pale conjunctivae , no icteric sclerae, no cervical and axillary lymphadenopathy.

Pulmonary system: Equal breath sound, no adventitious sound

CVS: Regular rhythm, normal S1S2, no murmur, PMI at 5th ICS MCL

Abdomen: Normal contour; soft, not tender; normoactive bowel sound; liver 1 cm. below RCM with span 12 cm., blunt edge, rubbery consistency; spleen just palpated

Extremities: Mild pitting edema at dorsum of feet

Neurological Examination:

Good consciousness, cooperative

Cranial nerve: Pupils 3 mm. with reaction to light; no exudates or hemorrhages; other CNs were normal

Motor Upper extremities No fasciculation, no atrophy Tone: Normal

Power: grade V all Reflex: 2+ all

Lower extremitiesNo fasciculation, no atrophy Tone: mild hypotoniaPower:

EHL, Tibialis anterior (Rt./Lt.): I/II

Finger flexors (Rt./Lt): I/II

Ankle extensor (Rt./Lt.): I/III

Ankle flexor (Rt./Lt.): I/II

Ankle inversion (Rt./Lt.): II/III

Ankle eversion (Rt./Lt.): II/III

Reflex: 0+ all

Babinski’s sign: Plantar responseClonus: Negative

SensoryUpper extremities

Pinprick sensation: Normal

Proprioception: Normal

Lower extremities

Pinprick sensation: Decreased all toes

Proprioception: Loss of joint position sensation of both feet;

Romberg: positive

Hyperesthesia of both plantar sides

ANSAnal sphincter tone: Normal

Anal reflex: Normal

CerebellumFTN: normal, no dysdiadocokynesia, no trunkal ataxia

Tandem gait: can’t be evaluated

No meningeal sign

2+2+

2+

2+

2+

2+

00

00

Motor : weaknesshypotoniaPinprick

Proprioception / Hyperesthesia

Problems• Neurological

– Abnormal sensation of lower extremities• Pinprick

• Hyperesthesia

• Proprioception

– Motor weakness of lower extremities R>L and hypotonia

– Areflexia

• Non neurological– Weight loss

– Hyperpigmentation

– Hepatosplenomegaly

– Hyperuricemia (Hx)

The Nervous system• CNS

– Brain

– Spinal cord

• PNS

– Nerve

• Nerve root (Cauda equina)

• LS Plexus

• Peripheral nerve

– Mononeuropathy

– Multiple mononeuropathy

– Polyneuropathy

– NMJ, Muscle

ANS spared

Non root distribution

Discrepancy of motor,

sensory

Infiltrative ?Immune ?

Asymmetry

Hx and PE

Multifocal neuropathy

Mononeuropathy

Peripheral neuropathy

EMG

Axonal

Demyelination

Approach to Peripheral Nerve Disease

Axonopathy Demyelination

Motor Distal Proxima/ Distal

Sensory (pinprick)

Distal, Gloves and stockings

Not well demarcated

Proprioception Intact Impaired

Reflexes Decreased distal

Decreased generalized

Autonomic May involve Rarely

Length dependent

Axonopathy VS Demyelination

Impression:

Bilateral sural sensory, bilateral tibial, peroneal motor responses were absent.

Right median, ulnar motor responses showed prolonged distal latencies; slow

conduction velocities; prolonged F wave latencies.

The above studies are consistent with severe demyelinating polyneuropathies; lower extremities more affected than upper.

Hx and PE

Multifocal neuropathy

Mononeuropathy

Peripheral neuropathy

EMG

Axonal

Demyelination

Approach to Peripheral Nerve Disease

Investigations:

Complete blood count: White blood cell 10,121 (Neutrophils 71%, Lymphocytes 24%, Monocytes 5%), Hemoglobin 15.1, Hematocrit 44%,

MCV 73.6, MCH 25.4, MCHC 34.5, and adequate platelets counts

Urine examination: Clear yellow, pH 6.0, Sp.gr. 1.015, WBC 0-1, RBC 0-1, Protein trace, Sugar negative

Blood chemistry: FBS 97, BUN 12 , Creatinine 1.2, Sodium 144, Potassium 5.3, Chloride 110, Carbon dioxide 25, Albumin 4.4, Globulin 3.4, Total bilirubin 0.51, Direct bilirubin 0.11, SGOT 10, SGPT 5, Alkaline phosphatase 72, uric acid 7.3, Calcium 8.2, Phosphate 3.8, CHO 140, HDL 31, TG 180, LDL 80, LDH 430

Thyroid function test:

FT3 3.48 pg/ml (2.39-6.79)

FT4 0.90 mg/dl (0.58-1.64)

TSH 4.36 uIU/ml. (0.34-5.6)

CEA (Carcinoembreonic Antigen): 0.57 ng/ml (<4)

Vitamin B12 level: 300 pg/mL (243-894)

Anti-HIV: Negative

ESR: 11 mm/hr. (<20)

Serum VDRL: Non-reactive

HBsAg: Negative

Anti-HBc : Positive

Anti-HBs: Positive (55.9 mIU/mL)

Anti-HCV: NegativeANA: Negative

Cerebrospinal fluid study:

Open pressure 12 cmH2O

WBC 0, RBC 210

Protein 147 mg/dL

Glucose 56 / BS 92 mg/dL

CIDP

Lewis -Sumner

CIDP in systemic diseases

CIDP-DM

Sensory variant

SIDP

CIDP with CNS demyelination

CIDP-MGUS

MMN

DADS IgM/antiMAG

POEMS

CANOMAD(Chronic inflammatory

demyelinating polyneurpathy)

Typical CIDP

Motor : symmetrical proximal and distal limb weaknessSensory : symmetrical loss of proprioceptionand distal loss pinprick sensation

Autonomic : spared

Chronic progressive > 8 weeks or relapsing remitting

Clinical presentation

Typical CIDP

Investigations

High CSF protein in 80-95%

Electrodiagnosis demyelinating polyneuropathy

Nerve biopsy is rarely needed

R/O CIDP mimics

Treatments

good response to immunomodulating therapies

Problems• Neurological

– Abnormal sensation of lower extremities• Pinprick

• Hyperesthesia

• Proprioception

– Motor weakness of lower extremities R>L and hypotonia

– Areflexia

• Non neurological– Weight loss

– Hyperpigmentation

– Hepatosplenomegaly

– Hyperuricemia (Hx)

Abnormality Neuropathy

Ulcerations Hereditary sensory and autonomic neuropathies, diabeticHypopigmentation Sarcoid, leprousHyperpigmentation POEMS, adrenomyeloneuropathy, cobalamin deficient

eosinophilia-myalgia syndromePurpura Cryoglobulinemic neuropathy (vasculitis)Livido reticularis Cryoglobulinemic neuropathy (vasculitis)Ichthyosis Refsum diseaseAngiokeratomas Fabry diseaseVesicles and bullae Variegate porphyriaAlopecia Hypothyroid, systemic lupus erythematosus, thalliumCurly hair Giant axonal neuropathyMees’ lines Arsenic and thallium toxicityWhite nails POEMS*Clubbing POEMS*, paraneoplastic (lung cancer), neuropathy with

pulmonary disease, Neuropathy with cirrhosis, neuropathy with inflammatory bowel disease

Skin, Hair, and Nail Changes Associated with Peripheral Neuropathies

Hyperpigmentation POEMS

adrenomyeloneuropathy

cobalamin deficient

eosinophilia-myalgia syndrome

Paraproteinemic Disorders associated with Neuropathy

•Multiple myeloma•Waldenstrom macroglobulinemia•POEMS (Osteosclerotic myeloma)•Amyloidosis•Cryoglobulinemia•Lymphoma (Castleman’s disease)

Ultrasound upper abdomen:

Mild-to-moderate hepatomegaly with mild increased echogenicity of liver parenchyma, no space-taking lesions, and no intrahepatic and common bile duct dilatation; no gall stone; moderate splenomegaly with mild increased echogenicity; no ascites; and no lymphadenopathy

Echocardiography:

All valvular structures appeared normal.

All cardiac chambers were not dilated. Good LV systolic function (LVEF 80% by Teich) without RWMA. RV normal contraction.

Doppler and color flow study showed normal.

Neither intracardiac thrombus nor pericardial effusion was detected.

P olyneuropathy

O rganomegaly (liver, spleen, lymph nodes,

cardiomyopathy)

E ndocrinopathy (diabetes mellitus, hypothyroidism,

gynecomastia, impotence, amenorrhea, elevated FSH)

M onoclonal gammopathy (M-spike)

S kin changes (hypertrichosis, hyperpigmentation, diffuse

skin thickening, hemangiomas, white nail beds)

Other features: wt loss, clubbing of fingers, peripheral edema, ascites, papilledema polycythemia, leukocytosis, thrombocytosis

POEMS Syndrome (Crow-Fukase Syndrome, Osteosclerotic myeloma)

Resembles CIDP with proximal and distal Weakness

Hypo-or areflexia

Large-fiber sensory loss (proprioception and vibration > pain and temperature)

Autonomic fibers spared

Cranial nerves spared (except for occasional papilledema)

Chronic, slowly progressive courses

Electrophysiologic features may be predominatly axonal or demyelinating

Clinical Features of the Neuropathy of Osteosclerotic Myeloma

Criteria for Diagnosis POEMS

Bone lesions in POEMS

• Osteosclerotic only 54-94%

• Mixed sclerotic and lytic 31-59%

• Lytic only 0-13%

• Solitary lesion 41-45%

• 2 or 3 lesions 23%

• >3 lesions 32%

Clinical diagnosis

• POEMS syndrome

Criteria for Diagnosis POEMS

• Serum protein immune electrophoresis:

Monoclonal gammopathy IgG ,lambda type

light chain

• Serum free light chain-kappa 59.3 mg/L

(3.30-19.40)

• Serum free light chain-lambda 55.5 mg/L

(5.71-26.30)• IgG 1990 mg/dL (700-1900)

• IgM 224 mg/dL (40-230)

• IgA 307 mg/dL (70-400)

• B2 Microglobulin 2461.2 ug/L (670-1310)

• Bone marrow aspiration: Hypocellular

marrow, plasma cell 8%

• Bone marrow biopsy

– Plasma cell neoplasm, mature plasma cells,

diffuse involvement.

Thank You…