Thread by @realbrainbook

Hi all, welcome to the second of this year's #neurosurgical case-based discussions. We're very lucky to have both @eacp and @mrmikehart as moderators tonight.. Lets get started

1. Ernest is a 62-year-old man who is returning to his neurology clinic for a check-up. His main symptom has always been a left sided tremor. But what exactly is a tremor?

2. Tremor is the most common disorder of movement. It is an involuntary rhythmic oscillation of one or more body parts. Whilst tremor commonly affects upper limbs it can also affect head, chin, voice, and legs.

3. Aside from different body parts affected, how else can we classify tremors?

4. Resting tremors and action tremors. Resting tremors occur when a body region and related muscles are relaxed, such as a hand resting in a lap whilst resting. Action tremors occur during voluntary muscle contraction.

5. Action tremors can be subdivided into postural, kinetic, and isometric. Postural occur during maintenance of posture, usually against gravity. Kinetic tremors occur during active movement. Isometric tremors occur in muscle contraction without movement.

6. So, what causes tremors? (Post your answers below :D)

7. Loads of things! Action tremors are very common but have a wide range of causes. ‘Essential tremor’ which involves both hands with or without head and voice involvement. Essential tremor is the most common form of tremor.

8. Action tremors may also be simply due to physiological tremor enhanced through intake of stimulants, withdrawal of alcohol, stress and fatigue. Other medical conditions such as hyperthyroidism can cause action tremor too.

9. A further important cause of action tremor is a cerebellar tremor, this can result from any lesion of the cerebellar pathways (trauma, stroke, MS).

10. Contrastingly, resting tremors are strongly associated with Parkinson’s Disease (PD) or other parkinsonian syndromes such as Lewy Body dementia, multiple system atrophy, or progressive supranuclear palsy.

11. Thats enough about tremors for now. Let’s continue with the case...

12.Ernest walks into the clinic room. You notice he has a slow shuffling gait with little arm swing. You examine him and find a 4-6hz resting tremor of the left hand, rigidity in passive movement of his limbs and a rachety ‘cogwheel’ movement when supinating/pronating his wrist

13. What is your top differential?

14. John is displaying the cardinal motor symptoms (bradykinesia, rigidity and tremor) of Parkinson’s Disease. Can you think of any other key symptoms of Parkinson’s Disease?

15. Mask like face, micrographia, hypomimia, hoarse or quiet voice, hoarseness of voice are other, less common symptoms of Parkinson’s disease.

16. Examination should also assess eye movement, ataxia or other cerebellar signs, or postural stability in early disease. The presence of these symptoms may suggest atypical Parkinson’s syndrome.

17. Ernest also reports he continues to have low mood. How common is depression in Parkinson’s Disease?

18. 40% of patients with Parkinson’s disease experience depression at the time of, or after diagnosis. Anxiety and panic whilst less common can also be a major problem for some patients. Mood disorder in PD is unfortunately, poorly understood.

19. So, what causes Parkinson’s Disease!?

20.Parkinson’s Disease is associated with neuronal loss in the pigmented brainstem monoaminergic nuclei. Specifically, dopaminergic neurons in the substantia nigra and noradrenergic in the locus coeruleus. Loss of these nuclei are directly linked to the motor symptoms of PD.

21.Parkinson’s disease is not just limited to these areas however, other areas of the brain stem, cerebral cortex, hypothalamus, sympathetic ganglia and olfactory tract are commonly involved.

22.To reduce these symptoms Ernest takes Levo-Dopa. This is metabolised within the brain to dopamine and replaces the deficiency in dopamine caused by the loss of dopaminergic cells.

23. What is Levo-Dopa? Do you know of any issues with levo-dopa as a medication?

24. Levo-Dopa is a substance the body can metabolise into dopamine. Over time patients experience a threshold effect for dopamine transmission. This results in an ‘all or nothing’ effect creating fluctuation in symptoms with akinetic ‘off’ periods and dyskinetic ‘on’ periods

25.Ernest wonders whether anything can be done to reduce these troublesome ‘on/off’ periods and improve his symptoms.... What other treatments are available for Parkinson's disease?

26.There are medical and surgical treatments for the treatment of Parkinson’s Disease.

27.Medical therapies focus on increasing the availability of dopamine by stimulating remaining cells to produce more dopamine (antagonists), supplementing with substances that are metabolised into dopamine (levo-dopa) or preventing its metabolism (MAO-B and COMT inhibitors).

28. These medications can be taken alone, or together in combination, to maximise reduction in symptoms whilst avoiding side effects of single medications taken at high doses.

29.Most patients with PD take these medications as tablets (orally). However in advanced PD or patients with significant motor fluctuations a more continuous method of administration is required...

30. Two solutions to this are: Apomorphine and Duodena. Apomorphine is (dopamine agonist) given as subcut injections throughout the day, or via continuous pump. Duodopa (dopamine replacement) gel is continuously fed into the proximal jejunum via a gastrojejunostomy tube (picture)

31. By giving these medications continuously, stable plasma levels can be achieved, and therefore motor fluctuations are reduced...

32.Surgical options for Parkinson’s Disease involve lesioning or deep brain stimulation. Lesioning involves the targeted destruction of areas within the brain to reduce symptoms. It was performed for many years but has now largely been replaced by Deep Brain Stimulation…

33. But what exactly is Deep Brain Stimulation?

34.Deep Brain Stimulation is a functional neurosurgical procedure that involves the implanting of electrodes into the brain in conjunction with a pacemaker that delivers high frequency electrical pulses.

35. What problems can we treat with DBS?
Parkinson’s disease is the most common indication for DBS. But we are also able to treat other movement disorders including dystonia and essential tremor. Research into other uses including epilepsy, OCD and mood disorders is ongoing..

36. How does Deep Brain Stimulation work? Whilst it is not entirely understood, the pulsations from the stimulator (aka. Implantable Pulse Generator) device appear to disrupt pathological neural discharges which in turn reduce the symptoms of PD or other movement disorders.

37.Which areas are commonly targeted for DBS for Parkinson’s Disease?

38.The subthalamic nucleus (STN) and Globus Pallidus Internum (GPi) are the most common target areas for PD. The thalamus is also used as a potential target though this is less common.

Why do we use different targets for DBS in PD patients? @eacp @mrmikehart

39.What are the benefits DBS surgery? For patients, such as Ernest, DBS can provide significant improvement in motor symptoms and fluctuations. It can provide relief for a large range of ‘off’ symptoms, and reduce the quantity of levo-dopa required reducing ‘on’ dyskinesias.

40. What are the risks of DBS surgery? As well as the risks of undergoing anaesthesia, bleeding may occur in between 1-4% of cases, and infection of the system in approximately 2% of cases. There are also risks associated with calibration of the DBS system, more on this later...

41. Important question: How do we know which patients are appropriate for DBS?

42.This is not a simple process. Cases are decided on an individual level by assessing symptoms, dopa-sensitivity, cognitive function and mood and medical comorbidities as well as using brain MRI to assess for significant atrophy or other contraindications.

43. Patients with PD that have few or mild motor symptoms, whose symptoms do not respond to levo-dopa or with significant cognitive impairment, white matter damage or with significant other medical comorbidities, will not benefit from DBS and so are thought to be less appropriate

44.Who do you think is involved in assessing potential patients for DBS?

45.Cases are discussed by a multidisciplinary team including other neurologists, neurosurgeons, neuropsychologists, and specialist nurses.

46. Ernest’s case is discussed, and it is decided that he would be appropriate to undergo subthalamic nucleus DBS!

47.He completes his pre-operative work up, this includes an MRI and CT scan of his brain. Ernest will undergo DBS implantation in two stages. First the probes will be implanted, then in a second stage the stimulation device will be implanted..

TIMEOUT! (Just a quick reminder to let you know there will be a KAHOOT quiz at the end of the CBD, you can access it here: 04730128)

48. Let’s fast-forward the case to the day of Ernest’s first operation. Inside the operating theatre a large frame is screwed onto into his head. He is put to sleep and a CT scan of his head is performed.

49.What is this frame, and why is it required?

50. Deep Brain Surgery is performed using stereotactic surgical techniques, this requires the accurate targeting of desired structure (e.g. STN) within 3D space. To achieve this the frame is attached to the patient’s head and forms a fixed point of reference.

51. Pop quiz: Is deep brain surgery performed awake, or asleep?

52. Like a lot of medicine the answer is ‘It depends’. Some opt to perform DBS awake, others asleep. There is significant variation DBS procedures depending on centres this also includes differences in the type of intra-operative imaging or use of intra-op neurophysiology.

53. Returning to the case... Ernest returns from the CT scanner and is transferred to the surgical table. The surgical team using sophisticated software can now calculate the location of the target area (subthalamic nucleus).

54. The surgeon washes Ernest hair with surgical prep. A small amount of his hair is then shaved and two small incisions, one each side of the head, are made.

55.Using an electric drill, a small hole is then drilled into the skull. At the precisely precalculated depth the electrode is slowly and carefully placed. The same process is then repeated on the other side.

56.Each electrode is secured against the skull and attached to leads which are then buried under the skin. Ernest, still under anaesthesia, is returned to the CT scanner for a further scan to check the placement of the DBS probes.

57.The surgical team is pleased with the placement of the probes and Ernest is woken up from his anaesthesia and after recovering is returned to the ward.

58.Following implantation, can you think of any important complications to be aware of?

59.Intracerebral haemorrhage, ischaemia, and infection. A degree of asymptomatic intracerebral haemorrhage is acceptable and may be identified only through post-op imaging. Headache, N&V, or other symptoms of hypertension would require examination, re-imaging and further mngmt

60. Infection whilst not an immediate post-op concern is a significant risk. Whilst multiple steps are taken, including surgical scrub and prophylactic antibiotics. Infections require prompt antibiotics and in serious cases, removal of probes or DBS system.

61.A couple days later, Ernest returns to theatre and a implantable pulse generator (IPG) is implanted under the skin in his left chest. The leads are then tunnelled subcutaneously and connected to the stimulator.

62. Ernest awakes from his surgery, returns to the ward and the next day he is discharged to continue recovering at home.

63.Why is it important to wait following the operation before calibrating the DBS system?

64.The insertion of electrodes into the brain causes traumatic oedema and a mild lesioning effect, often patients experience improvement in their symptoms. It is important to wait for resolution of the oedema to enable accurate calibration.

65. Ernest returns to the clinic a few weeks later and undergoes DBS calibration. But what actually is calibration, and why does it matter?

66.The DBS electrodes implanted into the brain contain multiple separate controllable points of stimulation. During calibration the frequency, amplitude, pulse width (duration of pulse) and direction of stimulation is adjusted.

67.During calibration, Ernest experiences a strange tightening of the left side of his face, tonic contractions of his left arm and he is dysarthric. Looking at the anatomy in this image, can you see what has happened?

68. As you can see, the subthalamic nucleus is very close to the internal capsule (IC). The stimulation is inadvertently stimulating the internal capsule leading to these bizarre motor side effects.

69.The parameters of stimulation for Ernest’s DBS system is altered ensuring only the subthalamic nucleus is stimulated. His face, arm and voice symptoms immediately disappear.

70.Ernest’s calibration is completed successfully, he will need to return in future for check-ups and even recalibration. But for now he can continue to enjoy his retirement with his family and friends.

THATS A WRAP. Hope you enjoyed this quick run through of tremor, Parkinson's disease, and deep brain stimulation! Don't forget to check out the Kahoot quiz here (for a chance to win the grand prize!) kahoot.it/challenge/0473…

Also please do fill out a feedback form if you would like a certificate / evidence of CPD - forms.gle/3t56MdBo1aw2aF…

Finally, a huge thank you to @eacp and @mrmikehart for moderating, answering questions and chipping in with so many great pearls throughout!