XI. 근 신경계 질환(Neuromuscular disease)

8.hwp

XI. 근 신경계 질환(Neuromuscular disease)

목차

I. 총론

II. 전각 세포 질환(Anterior horn cell disease)

III. 말초 신경질환(Peripheral nerves)

IV. 신경 근 접합부 질환(Neuromuscular junction disease)

V. 근병증(Myopathy)

I. 총론

1. 정의

Disorders of Lower motor system including anterior horn cells, peripheral nerves, neuromuscular junction, muscles

2. 근신경계 질환의 감별

Table 1. Differential features of various neuromuscular diseases

	Anterior horn cells	Peripheral nerves	Neuromuscular junctions	Muscles
Disease entity	Motor neuron disease	Peripheral neuropathy	Myasthenia gravis	Myopathy
Distribution of involvement	Widespread	Distal part	Proximal part/Oculobulbar area	Proximal part
Sensory involvement	Absent	Present	Absent	Absent
Reflexes	Weak/Absent	Weak/Absent	Usually Normal	Usually Normal
Other signs	Fasciculation		Myasthenic symptoms
Serum muscle enzyme(CK)	Normal	Normal	Normal	Increased
Nerve conduction velocity	Normal	Slow	Normal	Normal
Needle EMG	Wide spread denervation	Denervation in distal muscles	Usually Normal	Myopathic MUP
Jolly test	Normal	Normal	Decremental response	Normal
Muscle biopsy	Denervation process	Denervation process	Non-specific	Myopathy

II. 전각 세포 질환(Anterior horn cell disease)

1. 정의

Neuronal degeneration confined to the anterior horn cells and motor neurons in cerebral cortex

2. 분류

척수근 위축증(Spinal muscular atrophy)

근위축성 측삭 경화증(Amyotrophic lateral sclerosis)

진행성 근위축증(Progressive muscular atrophy)

원발성 측삭 경화증(Primary lateral sclerosis)

3. 척수근 위축증(Spinal muscular atrophy)

1) SMA type 1(Werdnig-Hoffmann disease)

infantile onset, presented as floppy infant syndrome

2) SMA type II, III(Kugelberg-Welander disease)

childhood - juvenile onset

muscle weakness, atrophy; variable

3) Survival Motor Neuron 1 (SMN1) protein; Chromosome 5q12.2-q13

mutated in more than 95% of SMA

4) 감별진단

progressive muscular dystrophy( by EMG: neurogenic vs myopathic )

4. 근위축성 측삭 경화증(Amyotrophic lateral sclerosis)

Sporadic(90%) or familial(10%: Cu, Zn superoxide dismutase mutation)

Upper motor neuron sign + lower motor neuron sign

Progressive muscle weakness and atrophy in adult age, usually asymmetric

Bulbar involvement, respiratory muscle weakness(cause of death)

Should preclude other treatable disorder(cervical radiculomyelopathy, multifocal motor neuropathy....)

5. 진행성 근위축증(Progressive muscular atrophy)

Lower motor neuron sign only(ALS - upper motor neuron sign)

More benign course?

6. 원발성 측삭 경화증(Primary lateral sclerosis)

Upper motor neuron sign only

Relationship with hereditary spastic paraparesis ?

III.말초 신경질환(Peripheral nerves)

1. General consideration

Type of involvement: polyneuropathy, mononeuorpathy, mononeuritis multiplex

Associated with many etiologies and diseases

1) 다발성 신경병증(polyneuropathy)

Symmetric loss of sensory function(paresthesia, hypesthesia), motor function, or both

Usually begins in the distal part( feet->ankle->knee->hand)

DTR loss in early stage(esp, ankle->generalized)

Atypical manifestation may be possible(e.g. diabetic amyotrophy: proximal involve)

Figure 1. Approach to the evaluation of peripheral neuropathy

2) 단일 신경병증(mononeuropathy or mononeuritis multiplex)

: Asymmetric dysfunction of one or more large nerve(e.g. carpal tunnel syndrome)

2. 말초 신경병증의 진단적 접근

1단계: identify presence of peripheral neuropathy(by clinical finding)

2단계: identify type of peripheral neuropathy: polyneuropathy, mononeuropathy, mononeuritis multiplex(by clinical finding)

3단계: identify pathologic nature of neuropathy: axonal or demyelinating (by nerve conduction study)

4단계: identify specific etiology of neuropathy(by clinical and laboratory test)

3. 다발성 신경병증(Polyneuropathy)의 분류

1) Diabetes

2) Nutritional and alcoholics

: alcoholic, vitamine B₁, B₁₂, B₆, E deficiency

3) Immune-related

: GBS and varients, CIDP, multifocal motor neuropathy with conduction block, sensory neuronopathy, autonomic neuropathy

4) Vasculitic

: polyarteritis nodosa, Sjōgren syndrome, Wegener granulomatosis, RA, cryoglobulinemia

5) Paraproteinemia(IgG or IgA)

: multiple myeloma, POEMS syndrome, amyloidosis, monoclonal gammopathy of unknown significance

6) Paraneoplastic

: lung cancer, breast cancer, lymphoma, ovarian cancer

7) Amyloidosis

8) Infectious

: herpes zoster, CMV, HIV, diphtheria, Lyme disease, leprosy

9) Metabolic and endocrine

: renal failure, hepatic failure, hypothyroidism, acromegaly

10) Toxic

: metals, lead, arsenic, mecury, industrial agent

11) Drug-induced

: chloroquine, dapsone, disulfiram, metronidazole, nitrofurantoin, vinca alkaloids

12) Inherited

: CMT, HNPP, porphyria

4. 유전성 신경병증(Inherited neuropathy)

1) 유병율

Hereditary neuropathies: 30 per 100,000

CMT Type 1: 15 per 100,000

CMT 1A: 10.5 per 100,000

CMT 2: 7 per 100,000

2) Tissue involvement

(1) Demyelination

CMT IA, IB, III (Dejerine-Sottas), HNPP, Neuropathy with focally folded myelin sheaths, Congenital hypomyelinating neuropathy

secondary axonal loss occurs: Distal > Proximal, Major cause of weakness

(2) Axonal

: CMT type II; HMSN 5; HMSN 6

(3) X-linked CMT: may present with Demyelination, or Predominantly axonal loss

(4) Other hereditary motor-sensory neuropathies

often associated with complex clinical syndromes, or specific metabolic abnormalities

e.g. Friedrich's ataxia, Refsum's disease, Fabry's disease

5. Immune-related

1) Guillain-Barre syndrome(AIDP: Acute Inflammatory demyelinating polyneuropathy)

Acute onset motor weakness, paresthesia, pain, lower ext -> upper ext

Cranial nerve involvement: 75%, esp CN VII

Frequent autonomic dysfunction

Respiratory failure(up to 33%, require mechanical ventilation)

Albumino-cytological dissociation

Many variant (Miller-Fisher, PCB, motor axonal, pure sensory...)

2) CIDP(Chronic Inflammatory Demyelinating Polyneuropathy)

Similar to AIDP except relapsing remitting or progressive course over 2 months

Should preclude other Dx such as paraproteinemia, infectious, hereditary, etc

3) treatment: immunosuppression

6. Paraproteinemia

1) Polyneuropathy associated with serum M-protein

2) 원인:

Monoclonal Gammopathies of Unknown Significance (MGUS)

Cryoglobulinemia

Multiple myeloma

Osteosclerotic myeloma

Waldenstrom's macroglobulinemia

3) 임상 양상: similar to CIDP

4) POEMS syndrome

7. Paraneoplastic

1) Sensory neuronopathy

Antibody: Anti-Hu

Neoplasm: Small cell lung

2) Subacute motor neuronopathy

Weakness: Subacute; Arms > Legs

Neoplasm: Lymphoma

3) Sensory-Motor Neuromyopathy

Neoplasm: Many

Frequency ~ 5% of patients with cancer

8. Diabetes

Symmetric neuropathies

Chronic

Distal sensory±autonomic: most common

Autonomic

Sensory-motor

Acute

Painful

Reversible

Asymmetric neuropathies

Diabetic amyotrophy

Mononeuropathies

Mononeuritis multiplex?

IV. 신경 근 접합부 질환(Neuromuscular junction disease)

Figure 2. neuromuscular transmission

1. Neuromuscular transmission- figure 2. 참조

2. 신경 근 접합부 질환의 분류

ACQUIRED NMJ DISORDERS

Botulism

Myasthenia gravis

Autoimmune myasthenia gravis

Childhood MG

Drug-induced MG

Neonatal: Transient MG

Domestic animals

Myasthenic syndrome (Lambert-Eaton)

Snake venom toxins

CONGENITAL & FAMILIAL NMJ DISORDERS

Presynaptic defects

Synaptic defects

Postsynaptic defects: AChR disorders

Other hereditary MG syndromes

3. 중증 근 무력증-(Autoimmune)myasthenia gravis

1) 임상 양상

Weakness: Extraocular, Bulbar & Generalized

Fatigue

Onset: Adult or Childhood

May present with atypical clinical feature(e.g. similar to inflammatory myopathy)

2) Post-Synaptic dysfunction

Reduced Acetylcholine Receptors (AChRs)

Damage to Post-synaptic Membrane & Small NMJs

3) 진단적 검사

Tensilon

Serum Antibodies: IgG vs AChR, Anti-Striational with thymoma

Nerve Stimulation (RNS): Decrement, test proximal & facial muscles

Single fiber EMG: Increased jitter

4) Variants

Childhood

Arthrogryposis: Recurrent Congenital

Neonatal: Transient

Drug-induced

Sero-Negative: No detectable serum antibodies vs. AChRs

5) Associations

HLA types

Medications

Pregnancy

Thymoma in patients older than 30

Thyroid: Hyper- & Hypofunction

6) 치료: AChE inhibitors & Immunosuppression

4. Lambert-Eaton myasthenic syndrome

1) 임상 양상

(1) Weakness: Proximal > Distal, Legs + Arms (93%)

Respiratory: Rarely severe

Dysphagia (22%)

Improves with: Brief sustained exercise

May worsen with: Sustained exercise; Heat or Fever

Extraocular muscles: rarely involved on examination

Occasional ptosis

Symptomatic diplopia in ~ 40%: Transient

(2) Tendon reflexes:

At rest: Diminished or absent

Reappear after: Brief maximal voluntary contraction

(3) 동반 증후군

CNS, Ataxia, Encephalopathy

2) 병태 생리: Presynaptic disorder

Reduced numbers of P/Q Ca²⁺ channels on presynaptic terminals

Ultrastructure: Active zone particles on presynaptic terminals

3) Serum Antibodies

IgG vs Voltage Gated Calcium Channels (VGCC)

Cancer + LEMS: 98%

No cancer: 90%

4) Electrophysiology

Repetitive nerve stimulation: Increment After rapid (50 Hz) RNS, or Sustained muscle contraction

5) Tumor

(1) Frequency of association with neoplasm: Overall: 50%

(2) Associated neoplasms: Small Cell Lung Cancer(most common), Lymphoproliferative: Reticulum-cell sarcoma, T-cell leukemia, Lymphoma, Castleman's disease

(3) Other possible associations: Non-small cell lung, Prostate, Thymoma

V. 근병증(Myopathy)

1. Disease category

Inflammatory myopathy

Muscular dystrophies and myotonic syndrome

Congenital myopathy: central core disease, multicore disease

Inherited metabolic myopathy

Endocrine myopathies

Drug induced, toxic and nutritional myopathies

2. 근 이영양증과 근 긴장성 증후군(Muscular dystrophies and myotonic syndrome)

1) General consideration

Group of genetically determined myopathies characterized by progressive degenerative changes in muscle fibers, without primary abnormalities in the lower motor neuron

Classified by clinical feature, but some genetic loci have been identified(e.g. Duchenne type: dystrophin)

Characteristics	Duchenne	Facioscapulo- humeral	Limb girdle	Myotonic dystrophy
Sex	Male	Both	Both	Both
Age at onset	Before 5 years	Adolescence	Adolescence	Childhood or later
Initial symptoms	Pelvic	Shoulder girdle	Either	Weakness and/or myotonia
Facial involvement	No	Always	No	Always
Pseudohypertrophy	Common	No	Rare	Never
Progression	Rapid	Slow	Slow	Slow
Inheritance	XR	AD	AD	AD
Muscle enzyme	Very high	Normal	Normal or sl.↑	Normal
Abnormal ECG	Common	Rare	Occasional	Occasional
Myotonia	No	No	No	No

Table 2. Type of common muscular dystrophy

2) Type of common muscular dystrophy- table 2. 참조

* Other forms of dystrophy are less common and include oculopharyngeal dystrophy, progressive dystrophic opthalmoplegia, and late distal dystrophy of Welander, etc

** myotonia; impairment of normal muscular relaxation following voluntary contraction, or electrical or mechanical stimulation.

3. 염증성 근병증(Inflammatory myopathy)

1) 정의

Group of disorders characterized by muscular weakness, and often associated with clinical and pathological features suggestive of inflammation.

2) 분류

Idiopathic

Polymyositis

Dermatomyositis

Dermatomyositis or polymyositis associated with connective tissue disease

Inclusion body myositis

Paraneoplastic polymyositis

Polymyositis and myositis due to infection

Drug-induced polymyositis

Polymyositis associated with other disorders

Related disorders

Eosinophilic syndrome

Polymyalgia Rheumatica

3) Polymyositis

(1) 임상 양상

Muscle weakness: Proximal > Distal ,Symmetric

Selective regions of weakness: Dysphagia; Posterior neck; Quadriceps

Onset age: Usually > 20 years

Progression: Months

30%; Especially with associated connective tissue disease

(2) 동반되는 질환

Cardiac: Arrhythmias; Inflammatory cardiomyopathy

Pulmonary: Respiratory muscle weakness; Interstitial lung disease

Esophageal paresis

Malignancy: Mild increased risk

Autoimmune: lupus, Sjogren's syndrome, anti-phospholipid antibodies, thyrotoxicosis

(3) 검사

Serum CK: High (3 to 30 times normal)

EMG: irritative myopathy, small amplitude, brief, polyphasic motor units

Antibodies: disease specific & non-specific

Muscle Biopsy: myopathic change

(4) 치료

immunosuppression

4) 피부 근염(Dermatomyositis)

(1) 임상 양상

Skin: erythematous rash(heliotrope), periorbital edema

Muscle weakness: proximal, dysphagia

Joint contractures

Other occasional systemic features: ocular, cardiac

(2) 동반되는 malignancy

Lung and G-I tract in men, breast and ovary in women

Greater than polymyositis, esp age↑(>50)

(3) 검사

Serum CK: Normal or High (up to 30 times normal)

Antibodies: Mi-2 & Jo-1

Myoglobinuria (sustained): May be presenting feature

HLA types (Juvenile DM): B8, DR3 & A1 + B8 + DR3

EMG: irritative myopathy, small amplitude, brief, polyphasic motor units

(4) 병리소견

	Polymyositis	Dermatomyositis	Inclusion body myositis
Muscle fiber necrosis	Single fiber	Single or groups	Rare single fibers
Perifascicular atrophy	-	Present	-
Capillary numbers	Normal	Reduced	Normal
Microvascular change	-	Present	-
Inflammatory cell infiltrates	Endomysial	Perimysial, perivascular	Endomysial
CD8+ T cells	Common	Rare	Common
Rimmed vacuole and inclusions	-	-	Present

(5) 치료

Immunosuppressive treatment

Table 3 .Pathology of myositis