Saraf Tepi 2 Flashcards
Miopati
1
Q
Hipokalemi Periodic Paralysis
A
- autosomal dominant, bbrp sporadic
Terdapat dua tipe : 1. Tipe 1 : mutasi pada calcium channel CACNA1S pada kromosom 1q31 2. Tipe 2: mutasi pada sodium Chanel SCN4A
klinis : - episode kelemahan tanpa myotonia , dpt fokal Atau general
- hiporeflexia saat serangan
- serangan Dalam bertahan bbrp jam, dengan kelemahan lemah persisten selama bbrp Hari.
- diprovokasi Oleh : exercise, makan Kaya karbohidrat, ethanol, dingin, stress.
- pemeriksaan : serum kalium turun, CK Naik.
- tes provokatif dgn pemberian glukosa
Tatalaksana : - menghindari pencetus
- carbonic anhydrase inhibitor ; acetazolamid
- kalium-sparing diuretic
2
Q
Hiperkalemi Periodic Paralysis
A
- autosomal dominant, disebabkan mutasi sodium channel SCN4A
- periode kelemahan dipicu istirahat setelah exercise, puasa
- tes provokatif : pemberian kalium
- selama serangan dapat diberikan glukosa.
- Terapi preventif : thiazide diuretic
3
Q
Andersen-Tawil syndrome
A
- channelopathy , mutasi pada potassium channel KCNJ2 karakteristik : - kelemahan - ventrikular aritmia - gambaran distrofi
4
Q
Steroid induced myopathy
A
Penyebab : - penggunaan Obat obatan steroid - endogenous hipercortisolism , seperti sindrom cushing Pemeriksaan : - pemeriksaan EMG non spesifik - CK normal
5
Q
Centronuclear myopathy
A
Centronuclear myopathy terdiri atas 3 bentuk :
- Slow progressive infantile
- Severe-X linked neonatus; bentuk paling sering adalah myotubular myopathy
- Adult onset type
6
Q
Dystropic myotonia
A
Terdiri atas
1. Dystropic myotonia tipe 1 :
early adult life , ptosis & facial weakness, frontal balding, atrophy masseters & temporalis, Dan
weakness & atrophy otot tangan dan extensors
forearms & peroneal.
- Distal muscles are
characteristically affected.
- terdapat myotonia: phenomenon of prolonged contraction and slow relaxation.
- diaphragmatic weakness; respiratory failure, and cardiac abnormalities, especially
conduction defects
- Dystropic myotonia tipe 2 : proximal Myotonic Myopathy (PROMM). Klinis : Kelemahan otot proximal. Sering melibatkan cardiac, katarak.
7
Q
Congenital Muscular dystrophy; tiga tipe utama
A
Tiga tipe utama Congenital Muscular dystrophy:
(1) collagenopathies ; Ullrich’s CMD , Bethlem
myopathy
(2) merosinopathies ; laminin-α-2-related CMDs,
(3) dystroglycanopathies; Fukuyama CMD, muscle–eye–brain disease, dan Walker–Warburg syndrome.
8
Q
Fukuyama CMD, klinis Dan diagnosis
A
mutasi fukutin gene on chromosome 9q.
Klinis characteristic :
- weakness and ocular and CNS abnormalities.
- hypotonic
and floppy, with joint contractures at the hip, knee, and ankles.
- kelemahan dapat generalized, dan patients typically do
not learn to walk.
- Creatine kinase levels are elevated
- muscle
biopsy : dystrophic changes & reduced α-dystroglycan.
- sering melibatkan Central nervous system; cognitive developmental delay and seizures.
-Brain MRI : abnormalities in gyration and characteristic white matter changes
frontal region
9
Q
merosinopathy laminin-α-2 deficiency
A
- merosinopathy laminin-α-2 deficiency disebabkan mutation in the laminin-α-2 gene, which encodes for the protein
merosin - hypotonic saat Lahir
- severe weakness of the trunk and limbs.
- Extraocular and facial muscles are spared.
- Contractures pada kaki Dan panggul
- Some patients may have seizures; however,
unlike Fukuyama-type CMD, intelligence is generally preserved.
MRI shows white matter changes and sometimes cortical
abnormalities.
10
Q
facioscapulohumeral muscular dystrophy (FSHD)
A
- autosomal dominant ,deletions pada 3.3 kb repeating sequences, D4Z4, chromosome 4q35.
- slowly progressive, dan predominan pada wajah Dan bahu, extremitas bawah terkena pada stadium lanjut.
-Onset rata rata 16 in
males dan 20 in females, atau antara dekade 1 Dan 6 - Klinis :
- kelemahan dapat asymmetric, sulit mengangkat lengan ke atas kepala, dengan keterlibatan menonjol pada lengan atas
(scapular muscles, biceps, triceps, trapezius, serratus anterior, and
pectoralis), with relative sparing of the deltoids. upper arm
lebih atrophic daripada forearms, membuat tulang bahu menonjol. - Beevor sign : umbilicus moves upward with neck
flexion
11
Q
oculopharyngeal muscular dystrophy
A
- autosomal dominant late-onset muscular dystrophy with
manifestations restricted to the ocular and pharyngeal regions. - more frequent in patients of French-Canadian descent, disebabkan GCG repeat expansion pada poly-A–binding protein 2
gen chromosome 14q11.
Klinis : - dysphagia,
dysphonia, and slowly progressive ptosis, and sometimes late
involvement of extraocular muscles. - Tidak ada myotonia.
Pemeriksaan: - Creatine kinase and aldolase levels normal
- EMG abnormal in affected muscles.
- biopsi : demonstrates
variation in fiber size, rimmed vacuoles, and intranuclear tubular
filaments.
12
Q
carotid sinus hypersensitivity
A
- Carotid sinus
hypersensitivity results from an exaggerated response to
baroreceptor stimulation. - occurrence of syncope associated with either a
period of asystole of at least 3 seconds or a fall of at least
50 mm Hg in systolic blood pressure, dapat terjadi tanpa Bradikardi. - Triggers can include a tight collar, turning of the head, or even
swallowing
13
Q
Glycogenosis
A
Aglycogen storage disease(GSD/glycogenosis& dextrinosis) - is ametabolic disordercaused byenzymedeficiencies affecting eitherglycogensynthesis, glycogen breakdown orglycolysis(glucose breakdown), typically withinmusclesand/orliver cells Macam GSD 0 GSD 1 ; Von gierke disease GSD 2 ; pompe's disease/acid maltase deficiency GSD 3 ; Cori's disease/Forbes disease GSD 4 ; Andersen disease GSD 5 ; Mc Ardle disease GSD 6 ; Hers Disease GSD 7 ; Tarui Disease GSD 12; Aldolase A Defisiensi
14
Q
Mc Ardle Disease; klinis Dan diagnosis
A
: Glycogenosis tipe 5
: autosomal recessive; myophosphorylase deficiency. This enzyme normally participates
in the conversion of glycogen into glucose-6-phosphate; therefore,
its deficiency will lead to glycogen accumulation and lack of
glucose release from glycogen. The typical presentation is exerciseinduced weakness and muscle cramps. The muscle cramps are
physiologic contractures: they are electrically silent when an EMG
needle is inserted into the contractured muscles (this forms the
basis of the definition of true physiologic muscle contracture, in
contrast to chronic shortening of a muscle and its tendon which,
strictly speaking, is a pseudocontracture). Unlike normal muscles,
when the muscle is exercised there is no production of lactic acid
On exertion, a sensation of fatigue may ensue; however, if the
patient slows down or rests briefly, this sensation may disappear
and the patient may be able to continue with the exercise. This is
called a “second-wind phenomenon,” which is typically seen in
McArdle’s disease, and results from mobilization and use of blood
glucose
15
Q
Tarui Disease
A
Tarui disease (glycogenosis type VII) is caused by
phosphofructokinase (PFK) deficiency in muscle and erythrocytes.
This enzyme participates in the conversion of glucose-6-phosphate
into glucose-1-phosphate, and therefore, it is similar to McArdle’s
disease from the muscular standpoint. In addition, some patients
may develop jaundice (due to hemolysis) and gouty arthritis due to
PFK deficiency in erythrocytes. Immunohistochemical analysis
distinguishes these two disorders
16
Q
Cori’s disease
A
Cori’s disease (glycogenosis type III) is caused by a deficiency in
the debranching enzyme, leading to glycogen accumulation. These
patients can present with a childhood form with liver disease and
weakness or with an adult form characterized by myopathic
weakness.
17
Q
Andersen disease
A
Andersen’s disease (glycogenosis type IV) is caused by a
deficiency in the glycogen branching enzyme, and is characterized
by hepatomegaly from polysaccharide accumulation, cirrhosis, and
liver failure.
18
Q
Pompe’s disease / acid maltase deficiency
A
Pompe’s disease (glycogenosis type II) disebabkan acid maltase
deficiency, enzyme
participates in the breakdown of glycogen to glucose; its deficiency
leads to glycogen accumulation, causing the typical histopathologic
findings on muscle biopsy: vacuolated sarcoplasm with glycogen
accumulation that stains strongly with acid phosphatase.
19
Q
paramyotonia congenita
A
paramyotonia congenita, which is an autosomal
dominant channelopathy caused by a mutation in the sodium
channel gene SCN4A. The manifestations are similar to those of
myotonia congenita; however, unlike in myotonia congenita, in
paramyotonia congenita, there is no “warm-up” phenomenon.
Rather, repeated exercise accentuates myotonia, which is most
clearly appreciated in the eyelids. Hence the name is derived from
“para”-doxical reaction to exercise. Exposure to cold worsens the
myotonia and may precipitate weakness, also in contrast to
myotonia congenita. Percussion myotonia is rare, but can be seen
after exposure to cold. EMG after cold exposure can also
demonstrate fibrillation potentials followed by electrical
inexcitability
20
Q
Vaso Vagal Syncope
A
vasovagal syncope, a form
of neurally mediated syncope or neurocardiogenic syncope.
Syncope is a sudden transient loss of consciousness with a loss of
postural tone. There are several causes of syncope; one of the most
common causes is vasovagal syncope. It can have many potential
triggers, with phlebotomy being a common one. This type of
syncope results from a combination of inhibition of normal
vascular sympathetic tone and increased vagal tone. Clinical
features that suggest vasovagal syncope include preceding or
concomitant diaphoresis, palpitations, and nausea. It is more
common in women.
21
Q
Duschene Muscular dystrophy , klinis Dan diagnosis
A
presents early in life and manifests
with weakness and delayed development of motor milestones.
These children have frequent falls, and difficulty walking, running,
and rising from supine and sitting positions. Weakness is significant
in the proximal muscles, predominantly in the iliopsoas,
quadriceps, and gluteals, as well as the shoulder girdle and upper
limbs. It also tends to affect the pretibial muscles. These patients
have pseudohypertrophy of the calves due to fibrosis. They also
have scapular winging and contractures. Ocular, facial, and bulbar
muscles are usually spared. Cardiac involvement includes
arrhythmias, cardiomyopathy, and heart failure. It is recommended
that all patients with Duchenne muscular dystrophy undergo
cardiac evaluation
22
Q
Becker muscular dystrophy
A
Mirip dengan Duchene Muscular dystrophy namun dengan gejala lebih ringan Dan onset lebih tua (remaja Dan dewasa)
23
Q
Nonaka myopathy
A
Nonaka myopathy merupakan autosomal
recessive distal myopathy
- onset in early adulthood.
- characterized by foot drop associated with weakness of the anterior
tibial muscles. Eventually, muscles of the upper extremities are
affected, especially the extensors.
- Muscle
biopsy : rimmed vacuoles,
tubular filaments mirip inclusion body myositis,
Tanpa inflammation.
- This condition is associated with a mutation
in the GNE gene located on chromosome 9p
24
Q
Welander muscular dystrophy
A
Welander muscular dystrophy merupakan distal myopathy inherited autosomal dominant fashion,
- onset antara 40 and 60 thn
- usually begins with weakness and
atrophy in the distal muscles of the hands and later affects the legs. - Muscle biopsy :myopathic changes and rimmed
vacuoles
25
Markesbery–Griggs
Markesbery–Griggs merupakan autosomal dominant distal
myopathy
- onset later in adult life, disebabkan mutasi gene encoding titin chromosome 2q.
- Karakteristik: foot
drop ,kemudian berkembang wrist drop dan kelemahan extensor muscles of the forearms
26
Central Core Myopathy
Central core myopathy is an autosomal dominant disease, caused
by a mutation in the ryanodine receptor gene RYR1 on
chromosome 19q13.1. These patients are at risk for the
development of malignant hyperthermia and this should be
considered when general anesthesia is needed. The clinical
presentation is that of weakness and hypotonia soon after birth,
and subsequent delay in motor development. The weakness is
predominantly proximal, and the pelvic girdle is usually more
affected than the shoulder girdle. Facial, bulbar, and ocular
muscles are usually spared. Creatine kinase levels are slightly
elevated
27
Autonomic ganglionopathy
Symptoms of
autonomic ganglionopathy are due to dysfunction in the
parasympathetic and sympathetic nervous system;
orthostatic hypotension, absent heart rate variability , hypohidrosis or anhidrosis, dry mouth and
eyes, pupillary abnormalities, sexual dysfunction, early satiety,
constipation, and diarrhea due to abnormal gastric and intestinal
motility.
- It results from impairment of transmission of impulses in
the autonomic ganglia and affects both the parasympathetic and
sympathetic nervous systems.
-antibody against the ganglionic nicotinic acetylcholine receptor
- bisa
autoimmune / paraneoplastic ( small cell lung carcinoma
)
28
Miyoshi Myopathy
Miyoshi myopathy, which is an autosomal
recessive condition presenting early in adult life and manifesting
with weakness and atrophy in the distal leg muscles,
predominantly in the posterior compartment. The weakness may
eventually affect more proximal muscle groups. This condition is
caused by a mutation in the gene encoding dysferlin on
chromosome 2p. Mutations in dysferlin are also associated with
limb-girdle muscular dystrophy type 2B. Another mutation leading
to Miyoshi myopathy is in the ANO5 gene, reflecting the genetic
heterogeneity of this phenotype. Creatine kinase levels are
markedly elevated in the range of 10 to 100 times that of normal.
Biopsy shows dystrophic changes
29
Laing myopathy
; distal myopathy. Weakness begins in
the anterior tibial compartment and also affects neck flexors.
Eventually, finger extensors, shoulder and hip girdle muscles can
become involved but finger flexors and hand intrinsic muscles are
spared.
- The disorder is related to a mutation in myosin heavy chain
gene (MyHC 1 or MYH7, Chromosome 14)
30
Congenital Muscular dystrophy
At birth, these children are
hypotonic and weak, presenting with arthrogryposis, and may
develop respiratory insufficiency and bulbar dysfunction. With
time they may develop contractures and scoliosis. These patients
also have developmental delay and developmental anomalies of the
cerebral cortex. As a consequence of cortical involvement, seizures
occur in some subtypes of these disorders. Creatine kinase is
markedly elevated. EMG shows myopathic changes.
Histopathologically, there are dystrophic changes with
degeneration and regeneration of muscle fibers, and infiltration of
connective tissue. The congenital muscular dystrophies are caused
by genetic defects in sarcolemmal membrane proteins or
membrane-supporting structures
31
Bradbury–Eggleston syndrome
pure autonomic failure, also
known as Bradbury–Eggleston syndrome, which has been
attributed to loss of intermediolateral cell column neurons. It
results from deposition of α-synuclein in the autonomic nervous
system. Pathologically, Lewy bodies are seen.
Klinis :
typically impotence. Orthostatic (postural) hypotension (defined as
a reduction of systolic blood pressure by 20 mm Hg or diastolic
blood pressure by 10 mm Hg, or both), or a pulse rate increase of
20 bpm, is present, and is often worse in the morning, after meals,
exertion, and with heat exposure. Supine hypertension may occur
as well. Other features include hypohidrosis, nocturia, early satiety
and nausea (due to gastrointestinal hypomotility), urinary
hesitance and/or urgency with occasional incontinence, and neck
and shoulder aching (“coat hanger” distribution) precipitated by
standing
32
Statin induced myopathy
Statins are lipid-lowering agents that inhibit the 3-hydroxy-3-
methyl-glutaryl-coenzyme A reductase (HMGCR). Statins are
known to have muscle toxic effects, and the possible mechanism of
this adverse effect is by an action on the mitochondria and
sarcoplasmic reticulum, especially in type II muscle fibers. A
mutation in the gene SLCO1B has been associated with
predisposition to develop statin-induced myopathy (LDL receptor
gene mutations cause disorders of lipid metabolism, which statins
are used to treat)
Penggunaan bersamaan dengan fibrat Akan meningkatkan resiko.
Resiko lebih besar pada statin lipofilik (simvastatin, atorvastatin) daripada hidrofili (pravastatin,
rosuvastatin, and fluvastatin)
33
postural orthostatic tachycardia syndrome (POTS),
increase in
heart rate of at least 30 bpm from baseline, or more than 120 bpm
within 10 minutes of head-up tilt, without significant changes in
blood pressure, but with symptoms of orthostasis such as lightheadedness, palpitations, generalized weakness, visual changes,
headache, or tremor. The etiology of POTS is unclear; it is more
common in females, and symptoms worsen around menses,
suggesting a role for estrogen in the pathophysiology. Symptom
onset may follow a variety of triggers, including viral infection,
pregnancy, or surgery, and for this reason, autoimmune causes
have also been postulated. POTS can rarely be a manifestation of a
mutation in a norepinephrine transporter gene, which leads to
elevated plasma levels of norepinephrine, with subsequent
sympathetic overactivity. POTS may be comorbid with chronic
fatigue syndrome; the significance of this relationship is not clear.
In some patients with POTS, the symptoms are mild and do not
require treatment. In others, treatment may include β-blockers,
increased fluid and salt intake, fludrocortisone, and midodrine
34
Thyrotoxic periodic paralysis
Thyrotoxic periodic paralysis is a condition associated with
hyperthyroidism, thought to be present in genetically susceptible
patients but without a known gene mutation detected to date. It is
more common in Asians, with a male predominance. These patients
have episodes of proximal weakness and other manifestations of
thyrotoxicosis. During acute attacks, potassium should be provided.
β-blockers may be of benefit as prophylaxis. Carbonic anhydrase
inhibitors do not work
35
inclusion body myositis
inclusion body myositis affects adults usually older than 50 years.
- characterized by
asymmetric weakness and atrophy of the wrist and finger flexors, quadriceps, and anterior tibial muscles. Dysphagia can be present,
and there are no skin manifestations. Creatine kinase may only be
slightly elevate
Clinical manifestations include painless progressive weakness
that is more distal in the arms and proximal and distal in the legs.
Involvement of the finger flexors and flexor pollicis longus, leading
to thumb flexion weakness, with relative preservation of finger
abductors (the dorsal interossei) is a classic finding of IBM . although it does not occur in all patients. In contrast to
dermatomyositis and polymyositis, deltoid strength is typically
preserved in IBM
- Biopsi : endomysial inflammation, groups of atrophic fibers, and
intracytoplasmic vacuoles with granular material known as rimmed
vacuoles
36
Trichinosis
Trichinosis is caused by the intestinal nematode Trichinella
spiralis, which is transmitted by the ingestion of uncooked pork
containing the encysted larvae
Biopsi :
demonstrate the parasite and sometimes an
inflammatory infiltrate with eosinophils.
Treatment includes a combination of thiabendazole with steroids.
37
Nemaline Myopathy
Nemaline myopathy has phenotypic variability, with presentations
ranging from severe neonatal congenital forms to adult-onset forms
in which patients have proximal weakness, cardiomyopathy, and
prominent compromise of respiratory muscles. Neonatal forms
present with dysmorphic features, contractures, arthrogryposis,
generalized hypotonia, feeding difficulties, and respiratory
problems. There are other intermediate forms with infantile-onset,
childhood- and adolescent-onset forms
Histopathologically,
the fibers have rod-like structures that are seen beneath the
sarcolemma, also known as nemaline bodies or nemaline rods.
Type I fibers are smaller than normal and predominate
38
congenital acetylcholine receptor
deficiency/ congenital myasthenic syndrome
They most commonly present at
birth, but some forms do not present until childhood or early
adulthood. They are more common in males. The typical
presentation is one of ophthalmoparesis and ptosis in infancy, with
facial diparesis. Limb weakness and hypotonia are often present,
and respiratory involvement is rare but can occur. As in
autoimmune myasthenia gravis, in some forms of congenital
myasthenia, intravenous administration of edrophonium (a
peripheral reversible acetylcholinesterase inhibitor) transiently
improves symptoms, and there is symptomatic benefit from oral
acetylcholinesterase inhibitors as well. Because the congenital
myasthenic syndromes are not immune-mediated, there is no
response to immunosuppressive therapy or thymectomy
39
Acetylcholinesterase deficiency
Acetylcholinesterase deficiency is another congenital myasthenic
syndrome that presents with axial and respiratory weakness in
early infancy. Characteristically, patients have a delayed pupillary
response to direct light. Due to deficiency of the enzyme, these
patients do not respond to acetylcholinesterase inhibitors such as
edrophonium or pyridostigmine
40
transient myasthenic symptoms
In newborns of mothers with autoimmune myasthenia gravis,
transient myasthenic symptoms can occur due to transfer of
maternal antibodies to the fetus in utero. Signs of neonatal
myasthenia include hypotonia and poor feeding, with symptoms
improving typically within the first 2 weeks of life. This patient’s
symptoms and examination findings are still present at 6 months of
age
41
Emery–Dreifuss muscular dystrophy
–Dreifuss muscular dystrophy
X-linked form
results from a mutation in the gene encoding for the nuclear
membrane protein emerin. Thererequi autosomal dominant form in
which the gene affected, LMNA, encodes for the nuclear membrane
protein Lamin A
Klinis:
characteristically present with contractures, which can be seen at
the elbows, ankles, and neck. Muscle weakness tends to affect the
upper arms and shoulder girdle muscles first and later the pelvic
girdle and distal leg muscles. There is no pseudohypertrophy of the
calves, and intelligence quotient (IQ) is normal. Cardiac
involvement is prominent, with serious conduction abnormalities,
often requiring pacemaker placement
42
Ullrich’s congenital muscular dystrophy
Ullrich’s congenital muscular dystrophy,
which presents with neonatal weakness, contractures and distal
hyperlaxity, as well as protrusion of the calcanei. It is associated
with mutations in the collagen type VI gene, and is thought to be
related to Bethlem myopathy
43
Walker–Warburg syndrome
Walker–Warburg syndrome is an autosomal recessive condition
characterized by muscular dystrophy and brain and ocular
abnormalities. Patients are hypotonic at birth with elevated
creatine kinase levels. The ocular malformations include
microphthalmia, colobomas, cataracts, glaucoma, corneal opacity,
retinal dysplasia, and optic atrophy. There are multiple brain
malformations reported in this syndrome including hydrocephalus,
aqueductal stenosis, cerebellar hypoplasia, and cortical
abnormalities.
44
Muscle–eye–brain disease
Muscle–eye–brain disease is an autosomal recessive condition in
which there is also muscular dystrophy and brain and ocular
abnormalities; however, the cortical changes are milder and the
white matter changes are more focal. The eyes are also affected to
a lesser degree than Walker–Warburg syndrome
45
Myotonia congenita
two types of myotonia congenita: Thomsen’s disease,
which is autosomal dominant, and Becker’s disease, which is
autosomal recessive. This group of disorders is caused by a
channelopathy secondary to mutations in the voltage-dependent
chloride channel gene CLCN1 on chromosome 7q. The main
manifestation is myotonia, which is an impaired muscle relaxation
as seen when the patients cannot relax their handgrip after
grasping an object, and also manifested on percussion, leading to
contraction and delayed relaxation. Myotonic potentials can be
detected on EMG.
In myotonia congenita, as opposed to paramyotonia, there is a
“warm-up” phenomenon, in which the myotonia improves after
repetitive muscle activation.
Propofol and depolarizing neuromuscular blocking
agents may aggravate the myotonia, and patients may have
prolonged recovery. Mexiletine is the treatment of choice
46
Thomsen's disease
Thomsen’s disease merupakan myotonia congenita allelic to Becker’s
disease, tapi mutasi CLCN1 merupakan autosomal dominant
- onset dekade 1
- klinis : painless
myotonia, but not weakness, and is milder than the recessive form.
Becker’s disease is the recessive form that presents later, usually in
47
Bethlem Myopathy
Bethlem myopathy, which is an autosomal
dominant condition associated with mutations affecting the gene
encoding collagen type VI. These patients present with weakness
and contractures of the elbow and ankles, as well as
hyperextensible interphalangeal joints
48
Hirschsprung’s disease
Hirschsprung’s disease is due to maldevelopment of the
myenteric plexus with congenital absence. Most commonly, focal
congenital absence of the myenteric plexus in the internal anal
sphincter or rectosigmoid junction occurs, though in rare cases, the
myenteric plexus may be absent throughout the gastrointestinal
system. Segments of the colon that lack myenteric plexus cannot
relax, leading to fecal retention and distention of proximal colonic
segments. Some cases of Hirschsprung’s disease are due to
mutations in the RET proto-oncogene
49
Myofibrillar Myopathy
Myofibrillar myopathy is a congenital muscular dystrophy,
which may be autosomal dominant or recessive, and affects males
and females equally. It is characterized by slowly progressive
weakness of the muscles of the limbs and trunk, affecting both
proximal and distal muscles, but more the lower than the upper
extremities. Cardiac involvement with conduction abnormalities is
present in about 25% of the cases, and peripheral neuropathy can
also be seen. Hyporeflexia is frequent.
Causative mutations involve genes that encode for the proteins
myotilin, desmin, and αβ-crystallin. Pathologically, there is focal
dissolution of myofibrils and subsarcolemmal accumulation of
dense granular and filamentous material, variation of fiber sizes,
rimmed vacuoles, and central nucleation
50
Autoimun necrotising Myopathy
Several autoantibodies have been associated with a group of
disorders collectively known as the immune-mediated, or
autoimmune, necrotizing myopathies. Some statin-associated
necrotizing myopathies are caused by antibodies directed at 3-
hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase.
Another type of necrotizing myopathy is
marked by the presence of anti-signal recognition peptide (antiSRP) antibodies. Presence of anti-SRP antibodies is often associated
with statin use, though in such cases, the muscle pathology has
been attributed to autoantibody-mediated processes rather than
direct toxic effects of the statin on the muscle. Thus,
discontinuation of the statin does not typically lead to resolution of
the signs/symptoms
Klinis:
subacute
onset of predominantly proximal muscle weakness (though distal
muscle groups can also be involved), often with muscle
pain/tenderness and elevated creatine kinase. In anti–SRPassociated necrotizing myopathy, myonecrosis but with little or no
evidence of inflammation may be seen. EMG shows fibrillation
potentials at rest, increased insertional activity, short-duration
polyphasic potentials, and spontaneous and positive sharp waves.
Treatment is with immunosuppression
51
Neurogenic Orthostatic hypotension
as dehydration, are reversible.
Common irreversible causes are the neurodegenerative
parkinsonian syndromes such as multiple system atrophy (discussed
in Chapter 6) and Parkinson’s disease. In the latter, orthostatic
hypotension can be severe and warrants treatment.
Nonpharmacologic measures include (i) lower extremity
compression stockings which reduce venous pooling of blood in the
legs, and abdominal binders which help redistribute blood from the
splanchnic mesenteric circulation to the systemic circulation. (ii)
The patient is encouraged to increase fluid intake and ingest salt
liberally. (iii) To decrease nocturnal hypertension (from
pharmacologic therapies) and to reduce nocturnal diuresis, it is
recommended that patients place a wedge under the head of their
mattress bed during sleep.
Pharmacologic treatment options include (i) midodrine, a
vasopressor, (ii) pyridostigmine, a cholinesterase inhibitor which increases acetylcholine and acts at nicotinic ganglionic receptors,
(iii) fludrocortisone, a mineralcorticoid which expands plasma
volume and increases vascular α-receptor sensitivity, (iv)
droxidopa, which is converted to norepinephrine. All the
pharmacologic agents, with the exception of pyridostigmine, can
lead to significant supine hypertension
52
Hirayama disease / monomelic
| amyotrophy
Hirayama disease, also known as monomelic
amyotrophy. This condition presents in young patients of Asian
origin, and it is characterized by progressive asymmetric wasting
of one or both hands and forearms. Examination shows atrophy
and fasciculations with no sensory deficits. These patients have a
high incidence of atopic disorders
53
anesthesia paresthetica
Nitrous oxide toxicity.
Nitrous oxide is an inhalational anesthetic agent which produces
irreversible oxidation of cobalamin, and makes the
methylcobalamin inactive. The manifestations occur in patients
with underlying cobalamin deficiency even after a single exposure
to nitrous oxide, usually with a rapid onset of symptoms. neurologic manifestations include myelopathy,
neuropathy or even cognitive changes, and encephalopathy. MRI
changes with T2 hyperintensity c
54
Spinal muscular atrophy (SMA)
Spinal muscular atrophy (SMA) are a group of four
disorders of anterior horn cell degeneration.
SMA 1(infantile) / Werdnig–Hoffman disease
SMA 2; intermediate (1-2 thn)
SMA 3; juvenile / Kugelberg–Welander disease
SMA 4 ; adult/pseudomyopathic SMA
Serum creatine kinase may be significantly elevated
(more than 10 times normal), particularly in the younger-onset
forms. Sensory NCSs are normal; EMG shows evidence of acute and
chronic denervation and reinnervation, with large polyphasic
motor units. Complex repetitive discharges occur in SMA type 3.
Muscle biopsy shows atrophy of entire fascicles or groups of
fascicles, with normal or hypertrophied neighboring fascicles
55
Werdnig–Hoffman disease
SMA type 1, infantile
SMA or Werdnig–Hoffman disease presents with decreased fetal
movements, neonatal hypotonia, and weak cry. Patients with SMA
type 1 exhibit head lag and frog-leg posture when supine, and are
never able to sit up or achieve antigravity strength in the arms or
legs. Diffuse areflexia is often present. Bulbar involvement leads to
dysphagia, and respiratory involvement occurs. Death usually
occurs by 2 years of age.
56
Kugelberg–Welander disease,
SMA type 3, juvenile SMA or Kugelberg–Welander disease,
typically presents in childhood (between ages 5 and 15 years) with
difficult walking. The clinical picture is one of proximal muscle
weakness, a fine action tremor, and fasciculations. Patients often
remain ambulatory into adulthood
57
spondylotic myelopathy
Spondylosis is a degeneration of the spinal column, in
which there is formation of osteophytes which eventually lead to
compression of the spinal cord and nerve roots. Along with this,
there are also disc herniations and ligamentum flavum
hypertrophy, leading to narrowing of the spinal canal. Since the
degenerative process progresses slowly, the neurologic
manifestations develop insidiously, unlike acute cord compressions
in which the patient will have manifestations of spinal shock,
which include weakness below the level of the lesion with
flaccidity and hyporeflexia, sensory loss, and sphincteric
dysfunction.
58
radiation-induced myelopathy
radiation-induced myelopathyThere are two types of radiationinduced myelopathy, a transient and a delayed form. The transient
form happens early, approximately 3 to 6 months after the
radiation treatment, and presents with dysesthesias in the
extremities which eventually resolve without sequelae. The
delayed form occurs 6 months or greater following radiation
therapy, as in this case. The presentation is insidious with
paresthesias and dysesthesias of the feet, Lhermitte’s phenomenon,
and progressive weakness of the legs. Eventually, bowel and
bladder can be affected. The MRI shows increased T2 signal in the
affected regions, sometimes with heterogeneous gadolinium
enhancement. Steroids have been tried, however, the key is
prevention by minimizing the dose of radiation used.
59
Lathyrism
Lathyrism is a neurotoxic disorder presenting as a myelopathy with subacute spastic paraparesis. It is endemic in certain parts of
Ethiopia, India, and Bangladesh, and occurs from the consumption
of Lathyrus sativus, a legume (grass pea or chick pea) which
contains the toxin beta-N-oxalylamino-L-alanine. It is more
prevalent in poor populations
60
Konzo
Konzo is a type of myelopathy that presents with a spastic
paraparesis of abrupt onset, sometimes associated with
involvement of the visual pathways. It is most commonly seen in
certain parts of Africa and results from consumption of poorly
processed cassava which contains cyanide. It is more prevalent in
droughts and in poor populations
61
Epidural lipomatosis
Epidural lipomatosis is a condition in which there is hypertrophy
of extramedullary adipose tissue in the epidural space, and is
usually associated with chronic use of steroids. Patients present
with back pain and myelopathic findings. The treatment involves
stopping steroids, and sometimes even surgical decompression.
MRI of the spine demonstrates the fatty tissue within the spinal
canal producing spinal stenosis, which was not described in this
patient
62
adrenoleukodystrophy
adrenoleukodystrophy there are four main phenotypes; an
early onset cerebral white matter disease (adrenoleukodystrophy),
adrenomyeloneuropathy, isolated Addison’s disease, or
asymptomatic. In adrenomyeloneuropathy male patients begin
having manifestations around age 20, with slowly progressive
paraparesis, sensory neuropathy, problems with sphincter control,
mild hypogonadism, and mild cognitive impairment. Some patients
may develop hearing and visual impairment as well. Most patients
also develop adrenal insufficiency. Increased levels of VLCFA( long chain fatty acids ) in
plasma and cultured fibroblasts help in the diagnosis. Patients
require steroids for the adrenal insufficiency, however, this
medication does not have an effect on the CNS involvement. Very
early bone marrow transplantation may be a therapeutic option.
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Kennedy disease
Kennedy’s disease (X-linked spinobulbar muscular atrophy).
Kennedy’s disease typically presents in males beginning the fourth
decade of life. The clinical presentation includes motor weakness
often starting in proximal muscles associated with features of
lower motor neuron dysfunction such as atrophy and hyporeflexia.
Tremor, muscle cramps, and fasciculations are other features of
this condition. Fasciculations involving the face and perioral region
are present in the majority of patients. Later in the course of the
disease, evidence of bulbar dysfunction becomes apparent.
Examination may reveal gynecomastia, but its absence does not
preclude this diagnosis. Endocrine abnormalities, including
hypogonadism with sterility and diabetes, occur in some patients.
This disorder rarely manifests in females, likely due to random Xinactivation, but has been reported, presenting with bulbar
dysfunction. Kennedy’s disease results from expansion of a CAG
repeat in the androgen receptor protein gene on the X
chromosome. Genetic testing for this disorder is commercially
available. Treatment is supportive
