INTRODUCTION TO

CLINICAL NEUROLOGY

Prof. dr Tamara Rabi Žikić

 Neurology

Is biological – MEDICAL discipline

It is a branch of internal medicine

Deals with study of organic diseases of the
NERVOUS and partly MUSCULAR system
 It investigates causes and origin (ETIOLOGY)
 mechanisms of development (PATHOGENESIS)
 signs and symptoms, course, and prognosis
(SYMPTOMATOLOGY, CLINICAL PICTURE)
 ways of evaluation (DIAGNOSIS)
 elimination (PREVENTION) of diseases of the NS
 treatment (THERAPY)
Considering the complex structure and function of the
nervous system, it is clear that understanding and
interpreting symptoms and signs of its damage
require special skills !
 Significance of
anamnesis and physical examination

Mechanisms of development,
clinical course,
type of symptoms and signs,
their localization
and presence of general signs
enables making conclusions about the
nature of disease
 Neurological diagnosis involves:

Anamnesis (main complaints, current

disease, personal and family history)

Objective examination of neurological,
psychological and somatic functions

Additional diagnostics
(biochemical, radiological, imaging,
ultrasonographic, neuropsychological,
histological, genetic, …)
 Neurological symptoms and signs
Lesions in the nervous system can be:
 Focal (IVC, TU)
 Multifocal or disseminated (ischemic stroke, MS)
 Diffuse (intoxication, atherosclerosis)

Neurological symptoms and signs can be:

 General (headache, disorders of consciousness, signs
of increased IBP) and localized (focal neurological or
neuropsychological deficit, disorder of vision, lesions
of CNS)
 Positive - excitatory symptoms (focal Epi, involuntary
movements) and negative (plegia, anesthesia, aphasia)
 Acute (up to 4 weeks) and chronic (muscular
dystrophies)
Approach to the neurological patient

First task is:

 Determining the site of damage:
on the basis of characteristic signs and symptoms of
lesions of individual parts of the NS

The complex neuroanatomy can be simplified to

 Nine major areas
muscle, neuromuscular junction,
peripheral nerve, root, spinal cord,
brainstem, cerebellum,
subcortical brain, and cortical brain
 Which symptoms determine
neuroanatomical localization?

 Asking target questions during

anamnesis (about disease onset and
course)
 Questions are asked systematically
from distal towards proximal
neuroanatomic parts:
from muscles to the cerebral cortex
 Objective examination confirms
anamnestic data
 Muscular diseases - etiology
HEREDITARY MUSCULAR DISEASES include
 Progressive muscular dystrophies

Hereditary disease, degenerative in nature, progressive
and symmetric muscle weakness

Classification is most commonly based on distribution of
muscle weakness and the type of inheritance
(Duchenne’s MD, Becker’s MD limb-girdle MD, distal MD,
occulofaringeal MD...)

ACQUIRED MUSCULAR DISEASES include

 Inflammatory myopathies – myositides: idiopathic,
accompanied by connective tissue disease, infectious:
viruses, bacteria, parasites, fungi
 Endocrine myopathies: found in dysfunction of the
hypophysis, thyroid, parathyroid and adrenal gland
 Myopathies: induced by medications, toxins, alcohol
 Muscular diseases- clinical picture
 Muscle weakness – proximal muscles of
extremities are characteristically affected
 Affected muscles – atrophic, may be also
hypertrophic due to proliferation of connective
and fat tissue
 Tone – can be flaccid, or elastic firm in
pseudohypertrophy
 Reflexes – in the beginning normal, later
diminished or absent
 There may be – pain (in myositis), cramps
(painful spasms), fatigability
 Sensation normal
 Muscle diseases - specific anamnesis

Proximal leg weakness:
Symmetric weakness

can the patient get up Does the weakness affect
from a chair or bed both arms or both legs?
without assistance or
using his hands?
Normal sensation !
Is there sensory loss?
Pain and cramping in

Proximal arm weakness: muscles may occur, but
can the patient lift or actual sensory changes
carry objects such as should exclude myopathy!
bags, young children,
books?
 Muscle disease – physical
examination

Examination reveals:

Symmetric proximal weakness

No sensory loss

Size of muscles: decreased (hypertrophy,

atrophy) or increased (pseudohypertrophy)

Tone – normal or mildly diminished

Muscle reflexes – usually normal till advanced

stages or mildly decreased
 Muscle disease: diagnostic methods

 Serum enzymes levels

(Creatine phosphokinase - CPK)
 EMNG
 Biopsy and PH analysis
 Mollecular-genetic study
Neuromuscular junction diseases
 Neuromuscular junction diseases:
etiology
 Congenital myasthenic syndrome – impairment may
be at presynaptic, sinaptic or postsynaptic level
 Acquired disease of neuromuscular transmission:
 Botulism – botulinum toxin prevents Ach release
and thereby causes presinaptic blockade
 Lambert-Eatonov sy - paraneoplastic or
autoimmune disease; at presynaptic level AT causes
decreased release of Ach
 Myasthenia gravis – autoimmune disease; AT at
Ach receptor causes postsynaptic blockade of n-m
transmission and leads to muscle weakness
 Clinical picture of
neuromuscular junction diseases :

Main symptom is muscle weakness

 proximal symmetric weakness,
no sensory loss
 Muscle weakness worsens with
activity and recovers with rest
is a highly specific characteristic of
neuromuscular junction disease
 Physical findings in
Myasthenia gravis:

Proximal symmetric
Upward gaze leads to:
weakness dropping of the eyelid

Repeated examination (ptosis)
reveals weakness that
Prolonged speech leads to
recovers with rest impaired articulation
(dysarthria)

Size of muscles is normal,

Weakness often involves
no atrophy and
muscles of the face, eyes
fasciculations, normal
and jaw
tone and reflexes

No sensory loss !
 Neuropathies: etiological
classification

Genetically determined
 Primary - gene mutation leads to pathological changes
in myelin and/or axon of peripheral nerves
 Secondary - as part of hereditary metabolic diseases

Acquired
 Immune-mediated, accompanied with vasculitis,
connective tissue disease, metabolic, endocrine,
nutritional, alcoholic, toxic, infectious, traumatic
 Neuropathies: clinical classification
Mononeuropathies
 Symptoms and signs of lesion to one peripheral nerve
 Consequence of trauma or part of systemic disease with
compressive lesions in physiological channels.

Multiple mononeuropathies
 Involvement of more than one peripheral nerve
 Asymmetric weakness and sensory loss in more than
one extremity and in distribution of more than one
peripheral nerve
 Etiology: vasculitides, DM, hypothyroidism, sarcoidosis,
leprosy, HIV, genetically determined
Polyneuropathies
 involvement of all peripheral nerves, usually symmetric
distribution
 Clinical classification of
neuropathies

Cranial neuropathies
 Lesion to one or more cranial nerves:
Lesion of facial nerve (idiopathic, in neuroboreliosis)
Lesion of occulomotor nerve (in diabetes)

Peripheral neuropathies
 Disease of peripheral nerves of extremities and trunk
 Neuropathy: symptoms and signs

Muscle weakness is:

 More frequently distal, accompanied by
 Atrophy
 Fasciculations and
 Sensory changes
 SYMPTOMS AND SIGNS OF NEUROPATHY:
MOTOR
 Loss of strength (paresis, paralysis), usually distally
localized, diminished tone, atrophy, absent reflexes
 Excitatory symptoms: fasciculations, muscle spasms,
cramps
SENSORY- abnormal sensitivity:
 Hyper/hypo/anesthesia, hyper/hypoalgesia
 Paresthesia (spontaneous sensation of burning,
pricking, numbing)
 Dysesthesia (unpleasant abnormal sensation produced
by a stimulus)
AUTONOMIC:
 Trophic changes on the skin and nails, orthostatis
hypotension, neurogenic bladder, constipation/diarrhea,
impotence, anhydrosis
 Peripheral neuropathy:
specific anamnesis

Distal leg weakness:

 Does the patient trip, drag his feet or have trouble
to step over low obstacles?
Distal arm weakness
 Does the patient frequently drop things or have
trouble with his grip?
Denervation changes
 Is there muscle atrophy or twitching within the
muscle (fasciculations)?
Sensory changes
 Has the patient felt numbness, tingling or
paresthesias?
 PHYSICAL FINDINGS IN
PERIPHERAL NEUROPATHY:
 Muscle weakness:

In polyneuropathies: there is distal weakness with
atrophy, fasciculations
Muscle tone is usually decreased.
Tendon reflexes are diminished or absent
 Sensory loss

In mononeuropathy – sensory changes in the distribution
of the affected nerve

In polyneuropathies – sensory changes in arms and legs -
“stoking and glove” symptom
 Due to frequent involvement of autonomic fibres
there may be trophic changes - smooth, shiny skin,
vasomotor changes such as swelling or temperature
dysregulation, loss of hair or nails.
 Etiology of root disease
(radiculopathies):

Degenerative changes of the spinal column
(intravertebral disk herniation, compression by
ostheophyte at intravertebral opening)

Trauma

Infection (ostheomyelitis, TBC, HIV, bacterial,
fungal meningoradiculitides,

Congenital anomalies

Neoplasms (primary or methastatis tumors)
 Radiculopathies: symptoms and signs

Radicular pain – intensive, sharp, stabbing or

burning, extending to affected deratomes or muscles
(myotomes)

Typically: pain worsens with strain (cough, sneezing,
defecation) , stretching (Lazarević sign) or movement.

Paresthesias in specific dermatome, especially its distal
part,

Decreased sensitivity for touch and pain in the affected
dermatome

Paresis of the muscle innervated by the affected root

Decreased or absent reflexes in the affected reflex arc

Fasciculations – rarely seen in radicular lesions
 Radiculopathies: neurological
findings

Physical examination reveals asymmetric

weakness with atrophy and fasciculations,
normal or diminished tone, decreased or absent
MTR

Sensory loss in the respective dermatome

 Spinal cord lesions

Symptom triad:
Sensory level is the

main and
 Sensory level pathognomonic sign
of spinal cord
 Distal symmetric disease
spastic weakness  Patients describe it
as a band or belt around
 Bowel and bladder their trunk or abdomen
sphincter below which sensitivity
dysfunction is decreased or absent
 Spinal cord lesions:
neurological findings

Superficial (skin) reflexes

Confirmation of may be absent
sensory level

Increased tone (spasticity)
below which all sensory and increased MTR (clonus)
modalities are diminished

Positive Babinski sign

Upper motor neuron
No significant atrophy or
damage: fasciculations
 More pronounced distal
Retention or
weakness on the same incontinence of urine,
side as the lesion less frequently stool
 Spinal cord lesion:
specific
specific anamnesis

 Distal leg weakness  Symmetric symptoms

Does the patient trip, Does the process involve the
arms and/or legs
drag his toes? approximately equally ?
 Distal arm weakness  Sensory level
Des the patient drop Is a sensory level present?
things or have trouble Patients often describe this
with his grip? as a band or belt around
their trunk or abdomen.
 Sphincter dysfunction
Retention or incontinence ?
(the bladder is involved more
often than the bowel )
 Syndromes of spinal cord lesion

Spastic quadriplegia, without lesion of VII CN-

lesion above C5

Flaccid arm paralysis and spastic leg paralysis –
lesion in the cervical spinal cord.
Spastic paraplegia – lesion of thoracic spinal cord
(below intumescencia lumbalis)

Flaccid paraplegia- lesion of lumbar spinal cord

L1-L5 and S1-S2
 Syndromes of spinal cord lesion

Conus medullarias lesion - lesion S3-5,Cg 1

Sensory loss - in the perianogenital region

“horse jockey pants”, sphincter dysfunction

Cauda equina sy – lesions in L2 and below

- Strong asymmetric radicular pains, asymmetric

flaccid leg weakness, “horse jockey pants”,
sphincter dysfunction
 Sydromes of spinal cord lesion

Brown-Sequard sy:lesion of one side of spinal cord

The same side as lesion

 Pyramidal type paralysis

 Anesthetic area at the level of lesion

 Deep sensory loss below the lesion

The opposite side to lesion

 Impaired pain and temperature sensitivity below
the lesion
 Spinal cord diseases

 Myelitis = inflammation of
spinal cord involving several
segments

 Polyomyelitis anterior acuta

(children’s palsy)
 Brainstem lesion

 Signs of cranial nerve

damage
 Signs of long tract
damage
Due to decussation of
“long” motor and sensory
tracts in the brainstem,
the lesion lead to
“vertical” signs -
hemisyndromes: pareses-
plegias; hypo-anesthesias.
 Brainstem lesion:
symptoms and signs

Brainstem lesions – produce “crossed

syndromes”- contralateral hemiplegia
and/or hemihypesthesia and ipsilateral
weakness of the cranial nerve.

Decussatio pyramidum lesions – there

may be lesion of one arm and
contralateral leg, or three paresis, or
tetraparesis.
 Brainstem:
symptoms and signs of damage

Lesions to cranial
nerves often
produce symptoms
referred to as
“Ds”: diplopia,
dizziness,
deafness,
dysarthria,
dysphagia,
dysphonia, ...
 Brainstem lesion:
neurologic findings

Lesions to CN+ long tracts = brainstem
disease

Examination of CN may reveal:
ptosis of the eyelid,
abnormalities of the pupil, bulbomotor
paralysis, diplopias, nistagmus, decreased
corneal reflex, weakness or spasm of mimic
muscles, deafness or impaired hearing,
vertigo, dysarthria, dysphagia,
weakness or deviation of the soft palate,
decreased maseter reflex, weakness of neck,
shoulder and tongue muscles.
 Brainstem lesions:
neurologic findings

Long tract damage:

 Produce weakness or paralysis of contralateral
or both sides of the body
 Signs of damage to central motor neuron and
distal weakness
 hyper-reflexia, spasticity and a positive
Babinski sign.
 Diminished or absent sensitivity in one or both
sides of the body in all modalities.
 Brainstem lesions:
specific anamnesis

Weakness or sensory loss in one side of

the body?

Diplopia, dysarthria-dysphonia,
dysphagia, dysmasesis, deafness,
vertigo, decreased sensitivity of the
face?
Functions of
the cerebellum

Maintaining body balance

Coordination of motor activities

Regulation of muscle tone
 Cerebellar lesion:
symptoms and signs are
 Ataxia
sitting, standing, walking (astasia-abasia)
 Ataxia of the extremities

Dysmetria:: inability to measure distance

Adiadochokinesis: inability to perform rapid alternating movements

Dysgraphia (megalographia)

Asynergia: impaired coordination of large muscle groups

 Inability to stop movement

Intention tremor: increased tremor when ending a movement

Braditeleokinesis: stopping far from the target location

Positive Stewart’s sign

 Dysarthria, nistagmus, hypotonia

 Cerebellar lesion
neurologic findings

 Staggering (ataxic) wide-based walk

 Inability to coordinate arm and leg movements
(“finger-nose” and “heel-sheen” tests) with slowing
down in front of the “end” (braditelekinesis).
 Rapid antagonistic movements are irregular in rate
and rhythm (dys/adiadochokinesis).
 Cerebellar lesion:
specific anamnesis

 Does the patient have a staggering walk?

 Does the patient have difficulty with targeted
movements with arms (placing a key in a lock, lighting
a cigarette)
 Are signs of brainstem damage present?
 Cerebellar disease may be accompanied by brainstem
abnormalities, since cerebellar inflow and outflow
must pass through the brainstem, and the same
blood vessels supply the cerebellum and brainstem.
Subcortical and cortical lesions

 Presence of specific cortical deficits

 Presence of motor and sensory
deficits
 Visual field deficits
 Cortical lesion

In the dominant hemisphere, produces:

aphasia, agraphia, alexia, acalculia, agnosia

In the nondominant hemisphere, produces:
 Visual-spatial problems and
 anosognosia – denial of own deficits
 Neglect of the opposite side
(inattention to own physical signs and symptoms)
 Motor deficits
in cortical and subcortical involvement

Depending on the part of the cortex involved,
there may be weakness of only one extremity
(e.g. faciobrachial or crural paresis or only
“central facial paralysis” )

Damage to the capsula interna- pyramidal fibers are

crowded in a small area, therefore even a small
lesion will produce masssive hemiplegia. Due to
proximity of sensory pathways, there may be
hemihypersthesias

Damage to the corona radiata – produces symptoms

that in range lay between cortical and capsular
 1. Leg
2. Forearm
3. Wrist
4. Hand
5. Thumb
6. Eye
7. Nose
8. Face
9. Lips
10. Tongue
11. Primary visual cortex
1. Cerebral cortex 12. Where images are first processed
2. White matter 13. Sex organs and feet
3. Myelinated fibers
4. Cerebeller "Tree of Life"
5. Internal capsule
6. Cranial nerves
7. Corona radiata
 Cortical sensory lesion
(parietal lobe lesion)
Cortical lesion
 Produces more subtle and complex impairments:
 Graphesthesia – inability to “read” numbers or letters on the skin
 Astereognosia – inability to recognize objects by touch
 Difficulty in localizing stimuli
 Impairment of tactile discrimination- inability to differentiate
between two subsequent/close stimuli
 Tactile inattention – inability to differentiate two stimuli in
different sides of the body

Subcortical lesion
 Leads to impairment of all sensory modalities
(touch, pain, hot, cold, vibration and position)
 Visual pathway lesion

Lesion of n. opticus – causes omplete blindness of the
affected eye

Incomplete lesion in front of the chiasm – scotomas or
narrowing of peripheral vision

Lesions behind the chiasm (where fibers from nasal
parts of the retina intersect) – produce symptoms in the
contralateral side of visual field of both eyes -
homonymous hemianopsia

Lesions of optic radiation – comprises a large area, so
partial lesions are possible - contralateral
quadrantanopia

Bilateral cortical lesion (lesion of the optical center) -
leads to “cortical blindness”.
AUTONOMIC NERVOUS SYSTEM
DISEASE
 AUTONOMIC NERVOUS SYSTEM
(ANS)

 Maintains visceral and

homeostatic functions of the
vital organs.

 Efferent component of the

ANS comprises two main
systems:
sympathetic and
parasympathetic
 ANS

Main parts of the CNS

involved in autonomic
regulation are::
• Insula

• amigdala

• Hyppothalamic
nuclei
• mesencephalon

• brainstem
 AUTONOMIC NERVOUS SYSTEM (ANS)

Efferent parasympathetic pathways are within

 cranial nerves (III VII, IX X)
• Innervate the lacrimal and salivary glands, heart, lungs,
gastrointestinal system
 output projections of sacral segments of spinal cord
(S2-S4)
• innervate the urinary tract, colon, reproductive organs

Most parasympathetic ganglia are located close to organs

they innervate
 CLASSIFICATION
OF AUTONOMIC DISORDERS

Primary - unknown cause Secondary - known cause

 Part of some degenerative  The most common – diabetic
diseases, such as PD autonomic neuropathy

Localized
Clear disorders  E.g. Horner’s sy
of the ANS
 Primary (idiopathic) Generalized
Degeneration of peripheral  Numerous different ANS

Segmenats of the ANS, problems

with no other neurological disorders
 Classification of disorders accompanied by
dysfunction of the ANS
• Inflammatory
Primary AD (GBS, Transversal myelitis)
Acute/subacut dysautonomy • Infectious
Syndromes of chronic disorder of (Bacteria–Tetanus, Viruses– HIV,
autonomic function Parasites–
Multiple system atrophy, Tripanosomiasis, Prions)
Autonomic Disorder associated • Neo - and paraneoplastic diseases
with PD, Clear autonomic
• Connective tissue disease
disorder
(SLE, Rheumatoid arthritis)
• Surgical procedures
Secondary AD (regional sympathectomy, vagotomy,
• Congenital
• Hereditary
organ transpalantation)
• Metabolic • Trauma (spinal cord break)
(DM, HBI, Chronic hepatic failure, • Other causes (Siringomyelia,
vitamine B12 deficiency, S.bulbia)
Alcohol-induced disorders) • Drugs, chemical compounds,
• toxins
 Main clinical manifestations in chronic
diseases of the ANS are
Urinary disorders
Orthostatic hypotension
and other CV disorders - Frequent and urgent
urination, involuntary
- Disorders of heart
voiding at night,
rhythm (paroxismal retention or incontinence
tachicardia in GBS,
bradicardia in brain TU - Respiratory disorders
or high lesions of - stridor, apneic crisis
cervical spine) Sexual disorders
Disorders of the GIT - Impairment of erection
- constipation, dirrhea, and ejaculation (may
dysphagia, gastroparesis precede for years other
Sudomotor disorders symptoms of autonomic
dysfunction)
- Anhydrosis
Anhydrosis or
hyperhydrosis
perhydrosis,, heat Visual disorders
intolerance - Horner’s sy, anisocoria
 Significance of anamnesis and
physical examination

Despite numerous and

precise neurological
diagnostic methods
(EEG, EP, US, CT, MRI,
PET, SPECT, CSF,
immunohistochemistry ...)
anamnesis and physical
examination are
irreplaceable in the
clinical work with
patients!